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processing and secretion of human carboxypeptidase e by c6 glioma cells.carboxypeptidase e (cpe) catalyses the removal of c-terminal basic amino acids and is implicated in the processing of peptides and hormones in secretory vesicles. the enzyme has been isolated in multiple forms from both soluble and membrane-bound compartments, and has been demonstrated to be co-secreted with peptides from pancreatic and adrenal cells. to address the question regarding the origin of the multiple forms of the enzyme, we have transfected a construct containing the cdna for human cp ...19911764034
single-dose administration of 9-(2-phosphonylmethoxyethyl)adenine (pmea) and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (pmedap) in the prophylaxis of retrovirus infection in vivo.9-(2-phosphonylmethoxyethyl)adenine (pmea) and 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (pmedap) are selectively inhibitory to human immunodeficiency virus and other retroviruses. we have now investigated the effects of different pmea and pmedap treatment schedules in newborn mice infected with moloney murine sarcoma virus (msv). administration of a single dose of pmea or pmedap on the day of msv inoculation conferred a greater protective effect against msv-induced tumor formation than whe ...19911776876
the expression of cathepsin b and other lysosomal proteinases in normal tissues and in tumors.the mrna for the lysosomal proteinases cathepsins b, d, h, l, and s are broadly distributed in normal rodent tissues. although total cathepsin mrna levels generally parallel the protein catabolic activity of the tissues, the expressions of the individual enzymes do not appear to be linked. thus, the relative proportions of the individual messages are found to vary from tissue to tissue. further evidence for the independent regulation of lysosomal proteinase expression is derived from observation ...19911801719
reduced stimulation of helper t cells by ki-ras transformed cells.a number of viral genes and cellular oncogenes inhibit major histocompatibility complex (mhc) antigen expression at the cell surface. in the case of inhibition of class i mhc antigens by viral genes this results in a reduced recognition by antigen-specific cytotoxic t cells. the activated ki-ras cellular oncogene carried by the ki-murine sarcoma virus (ki-musv) in contrast inhibits class ii mhc (or ia) antigen expression on transformed cells. we have studied how transformation with ki-ras affect ...19911826672
production and characterization of a monoclonal antibody to the v-mos oncogene protein.valuable information about proto-oncogenes and their physiological functions has been obtained by studying their expression in normal cells. however, the protein product of the c-mos gene, the cellular homologue of the transforming gene (v-mos) of moloney murine sarcoma virus, has not been detected in normal mouse cells or tissues. here, we have constructed a v-mos expression vector, pri-delta mos, which directs the synthesis of a truncated v-mos gene product, a protein a fusion protein. using t ...19911833309
moloney murine leukemia virus tolerance in anti-cd4 monoclonal antibody-treated adult mice.adult mice injected with moloney murine leukemia virus (m-mulv) 1 day after a short term treatment with anti-cd4 mab developed t cell lymphomas, or sarcomas when rechallenged with moloney murine sarcoma virus (m-msv). neoplastic development was correlated with virus spread, as thymic and peripheral t and b lymphocytes promptly expressed m-mulv-induced ag after virus introduction; no virus-specific ctl generation was detected in mltc. this failure, which was selective for m-mulv-induced ag, persi ...19911833453
phosphorylation of v-mos ser 47 by the mitotic form of p34cdc2.p85gag-mos is hyperphosphorylated during mitosis in normal rat kidney (nrk) cells transformed by moloney murine sarcoma virus ts110. we now report that p85gag-mos is phosphorylated in vitro by the mitotic form of the cdc2 kinase (p34cdc2, known as m-phase kinase) derived from virus-transformed cells. the major site of p85gag-mos phosphorylation by the m-phase kinase in vitro lies within the amino-terminal portion of the viral mos protein sequence spanning residues 45-53, as determined by tryptic ...19911833715
the specificity of the disease induced by defective murine retroviruses containing abl, fos, or ha-ras is usually not determined by their ltr.the long terminal repeats (ltr) of the defective murine sarcoma viruses (msv) containing v-abl, v-ha-ras, or v-fos were exchanged for ltrs from other retroviruses having different tissue tropism. the new chimeric msv were found to induce the same diseases as the parental viruses, indicating that sequences outside the ltr, most likely those of the oncogene, are responsible for the disease specificity of these defective msv.19911846504
myristylation alters dna-binding activity and transactivation of fbr (gag-fos) protein.fbr murine sarcoma virus (gag-fos) protein, a virally transduced fos protein, exhibits decreased gene transactivation in comparison with the cellular fos protein. biochemical analysis suggests that myristylation of the virally encoded n-terminal gag region results in decreased dna binding and transcriptional activation without affecting heterodimerization with jun protein. these findings demonstrate that protein myristylation can modulate gene regulation by a dna-binding protein.19911846672
derivatives of moloney murine sarcoma virus capable of being transcribed in embryonal carcinoma stem cells have gained a functional sp1 binding site.the long terminal repeat (ltr) sequences of moloney murine leukemia virus and its closely related derivative moloney murine sarcoma virus (mo-msv) are incapable of directing transcription in embryonal carcinoma (ec) stem cells. the myeloproliferative sarcoma virus, a derivative of mo-msv, has several point mutations in the ltr and is transcribed more efficiently to allow productive infection of f9 ec cells. one of these mutations, at -166 with respect to the transcriptional start, creates a cons ...19911848307
nickel mutagenesis: alteration of the musvts110 thermosensitive splicing phenotype by a nickel-induced duplication of the 3' splice site.we investigated dna damage caused by carcinogenic metals in a murine sarcoma virus (musv)-based mutagenicity assay in which mutations targeted to v-mos expression can be selected. nickel chloride treatment of nrk cells (termed 6m2 cells) infected with musvts110, a retrovirus conditionally defective in viral rna splicing and cell transformation, caused the outgrowth of transformed "revertants" with changes in the musvts110 rna splicing phenotype. cadmium and chromium treatment of 6m2 cells result ...19911848987
transduction of the cho aprt gene into mouse l cells using an adeno-5/aprt recombinant virus.an adenovirus-5 recombinant virus adapt1 carrying the chinese hamster ovary (cho) adenine phosphoribosyltransferase (aprt) gene was constructed by insertion of a 2.5-kb fragment containing the complete cho aprt structural gene linked to a moloney murine sarcoma virus (msv) promoter into the e3 region of adenovirus-5. the cho aprt gene was in the opposite orientation to the adenovirus e3 promoter. mouse lapt- tk- (lat) cells expressed the cho aprt gene when infected with the virus, even at low mo ...19911887332
inducibility of class ii major histocompatibility complex antigens by interferon gamma is associated with reduced tumorigenicity in c3h mouse fibroblasts transformed by v-ki-ras.paired lines of c3h mouse fibroblasts transformed with murine sarcoma virus (kirsten strain) were prepared that express high or low levels of class ii major histocompatibility complex antigen after treatment with interferon gamma (ifn-gamma). here, we described a comparison of the tumorigenicity of these lines in euthymic syngeneic and thymus-deficient nu/nu mice and in mice depleted of ifn-gamma. the class ii-inducible cells are clearly less tumorigenic than the noninducible cells in syngeneic ...19911898659
ligation of membrane ig leads to calcium-mediated phosphorylation of the proto-oncogene product, ets-1.recent studies have demonstrated that the nuclear protein, ets-1, which is preferentially expressed in lymphocytes, binds to the long terminal repeat of moloney murine sarcoma virus and htlv-1 and regulates gene expression. the association of ets-1 with dna has been shown to be lost when the protein is phosphorylated. thus, ets-1 may regulate gene expression in lymphocytes and this activity may be determined by its phosphorylation state. to address the possibility that ets-1 activity may be alte ...19911900874
viral kirsten ras infection differentiates pc12 cells and enhances their survival upon implantation into brain.neuronal cells from established cell lines can offer a well-characterized source of cells for transplantation to the brain that is an alternative to fetal neurons. the infection of members of the pc12 cell line with a retrovirus containing ras-oncogene leads to their neuronal differentiation without the need of nerve growth factor (ngf). we find that neoplastic, naive pc12 cells grafted to the striatum of normal adult rats cause the transient formation of large hemorrhagic cavities and do not su ...19911915724
retroviral transfer of a chimeric multidrug resistance-adenosine deaminase gene.a fusion between a selectable multidrug resistance (mdr1) cdna and an adenosine deaminase (ada) cdna concomitantly confers multidrug resistance and ada activity on transfected cells. we have produced a harvey murine sarcoma virus-derived, replication-defective, recombinant retrovirus to transduce this chimeric mdr-ada gene efficiently into a great variety of cells. infection with the mdr-ada retrovirus conferred the multidrug resistance phenotype on drug-sensitive cells, therefore allowing selec ...19901968408
response of mouse skin tumors to doxorubicin is dependent on carcinogen exposure.to investigate the role of carcinogenesis in determining the response of tumors to anticancer drugs, we have used the in vivo model of multistage carcinogenesis of the mouse skin. mice were initiated with harvey murine sarcoma virus or single and repeated applications of dimethylbenzanthracene (dmba). the papillomas which developed as a result of these initiation protocols were monitored quantitatively for their response to the anticancer drug doxorubicin. a single dose of 10 mg/kg doxorubicin i ...19901976437
reversible inhibition of a thyroid-specific trans-acting factor by ras.exposure of rat thyroid cells for 1 week to a temperature-sensitive variant of kirsten murine sarcoma virus (kimsv) ras inactivated the thyroglobulin promoter (ptg). cellular dedifferentiation was paralleled by the loss of the thyroid-specific trans-acting factor, tgtf1, which binds to ptg. when ras was denatured by shifting cells to 39 degrees c, tgtf1 binding and ptg function recovered rapidly without the synthesis of new protein. tgtf1 could be reactivated in vitro by treating nuclear extract ...19911989905
transformed rodent cells exhibit increased resistance to the carboxylic ionophores monensin and nigericin.rodent fibroblasts transformed with the kirsten and moloney murine sarcoma viruses exhibit increased resistance to the growth inhibitory and cytotoxic action of the carboxylic na+/h+ ionophore, monensin. the inhibitory effect of monensin on cell proliferation requires exposure for periods longer than 24 hours. the virus-transformed cells also exhibit increased resistance to the k+/h+ ionophore, nigericin. since monensin is known to have significant effects upon the function and activity of the g ...19911993049
cell-shape regulation and matrix protein p52 content in phenotypic variants of ras-transformed rat kidney fibroblasts. functional analysis and biochemical comparison of p52 with proteins implicated in cell-shape determination.the 52 kda transformation-sensitive protein p52 was previously identified as a major substrate-associated component of normal rat kidney (nrk) fibroblasts [higgins & ryan (1989) biochem. j. 257, 173-182]. p52 selectively localized to cellular fractions enriched in substrate focal-contact sites and associated ventral undersurface elements. rapid attachment/spreading of nrk cells on to prepared p52 matrices and inhibition of fibroblast spreading by antibodies to p52 indicated that this protein par ...19911996963
down-regulation of e-cadherin expression in madin darby canine kidney (mdck) cells inside tumors of nude mice.the 120-kda cell-cell adhesion molecule e-cadherin is localized at the epithelial junctional complex and participates in the organization and maintenance of epithelia. the madin darby canine kidney (mdck) cell line expresses e-cadherin in a stable way and forms polarized epitheloid structures in vitro. harvey-murine-sarcoma-virus-transformed derivatives (mdck-ras) produce malignant (i.e., invasive and metastatic) tumors in nude mice. we obtained evidence that e-cadherin is down-regulated in nude ...19912010235
nk and lak susceptibility varies inversely with target cell mhc class i antigen expression in a rat epithelial tumour system.several cell clones derived from cell lines obtained from a rat thyroid carcinoma, induced by in vivo injection of the kirsten murine sarcoma virus into thyroid gland, and from its spontaneous lung metastases were analysed for their major histocompatibility complex (mhc) class i antigen expression. the susceptibility to natural killer (nk) cell lysis of these clones, differing in their levels of mhc class i antigen expression, was determined and found to vary inversely with the target cell mhc l ...19912017656
concomitant alterations of microfilaments and microtubules in human epithelial cells (hbl-100) in relation to their malignant conversion.the organization of microfilaments and microtubules was studied in human epithelial hbl-100 cells at different steps in their malignant conversion. this conversion was obtained either spontaneously upon successive in vitro subcultures (approximately p. 70), or after superinfection of early passage non-tumorigenic cells (p. 28) with kirsten murine sarcoma virus. our results point out a clear relationship between the progression of cells toward malignancy, whatever the modality of malignant transf ...19912028179
in vitro differentiation of rhabdomyosarcomas induced by nickel or by moloney murine sarcoma virus.in vitro cultures and clonal derivatives have been established from rat rhabdomyosarcomas induced by moloney-murine sarcoma virus (msv) or by nickel sulfide; differentiation ability has been studied as expression of desmin, embryonic and adult myosin isoforms, alpha-actin isoforms and cellular fusion. the two rhabdomyosarcoma models showed different levels of myogenic differentiation. multinucleated myotube-like structures were frequently observed in cultures derived from nickel-induced tumours. ...19912039698
9-(2-phosphonylmethoxyethyl)adenine (pmea) effectively inhibits retrovirus replication in vitro and simian immunodeficiency virus infection in rhesus monkeys.9-(2-phosphonylmethoxyethyl)adenine (pmea) is a potent and selective inhibitor of the in vitro replication of a number of retroviruses, including hiv-1 and hiv-2, simian immunodeficiency virus (siv), simian aids-related virus (srv), feline immunodeficiency virus (fiv) and moloney murine sarcoma virus (msv). pmea causes a dose-dependent suppression of the induction of anti-sivmacgp120 antibodies in siv mac-infected rhesus monkeys. complete suppression of anti-sivmacgp120 antibodies was achieved i ...19912059358
expression of nf-l in both neuronal and nonneuronal cells of transgenic mice: increased neurofilament density in axons without affecting caliber.we have generated transgenic mice containing additional copies of the murine nf-l gene in order to examine the consequences of neurofilament-l overexpression on axonal morphology. founder mice were constructed to carry a transgene in which the presumptive 5' promoter sequences of nf-l were replaced with the strong murine sarcoma virus long terminal repeat promoter. the transgenes were expressed prominently in several tissues, including skeletal muscle and kidney where nf-l accumulated to approxi ...19902120242
potentiating effect of ribavirin on the in vitro and in vivo antiretrovirus activities of 2',3'-dideoxyinosine and 2',3'-dideoxy-2,6-diaminopurine riboside.2',3'-dideoxyinosine (ddi) and 2',3'-dideoxy-2,6-diaminopurine riboside (dddapr) are potent and selective inhibitors of human immunodeficiency virus (hiv) replication in mt-4 cells. they are also inhibitory to the transformation of c3h/3t3 cells by moloney murine sarcoma virus (msv). in vivo, they are only marginally effective in delaying msv-induced tumor formation, and mortality associated therewith in newborn nmri mice. when combined with ribavirin, ddi and dddapr become much more effective i ...19902123003
ras p21 onco-protein in the sera of mice carrying an experimentally induced tumor and in human cancer patients.we have established a model system to detect the presence of ras p21 in the sera of balb/c mice carrying tumors induced by a mouse cell line transformed with the harvey murine sarcoma virus in the presence of a helper friend murine leukemia virus. as determined by elisa and immunoblot assays, ras p21 in the serum increased with increased tumor growth. since ras genes have been found to be frequently activated in human tumours, we examined the levels of ras p21 in the sera of a variety of human c ...19902129802
cell cycle-mediated structural and functional alteration of p85gag-mos protein kinase activity.we investigated cell cycle-dependent regulation of protein kinase activity encoded by the viral mos gene by using a normal rat kidney cell line (nrk-6m2) chronically infected with a temperature-sensitive mutant (ts110) of moloney murine sarcoma virus, which produces the p85gag-mos transforming protein. in elutriation experiments, in which cells in various phases of the cell cycle are separated based upon size, a twofold increase in the specific activity of the p85gag-mos protein kinase was obser ...19902138725
the cyclin b2 component of mpf is a substrate for the c-mos(xe) proto-oncogene product.previous studies from this laboratory have shown that purified mpf from xenopus eggs contains cyclin b2 complexed with cdc2 kinase. the activation of mpf during oocyte maturation is known to require expression of the c-mos(xe) proto-oncogene. we show here that immunoprecipitates of either v-mos from moloney murine sarcoma virus-transformed nih 3t3 cells or c-mos from xenopus eggs phosphorylate cyclin b2 in vitro. phosphopeptide analysis reveals a pattern similar to that observed with cdc2 kinase ...19902140529
s-antigen and rod-opsin immunoreactions in midline brain neoplasms of transgenic mice: similarities to pineal cell tumors and certain medulloblastomas in man.transgenic mice expressing the large t-antigen of the simian virus 40 (sv 40) under the control of 1) the enhancer of moloney murine sarcoma virus (msv) and 2) the sv 40 promoter develop undifferentiated neuroectodermal tumors located in the midline of the dorsal brain surface, abnormalities in lens fiber differentiation and retinal dysplasia. in this study the brain neoplasms of six adult animals and the brain of one 11-day old mouse were examined by conventional histology and immunocytochemica ...19902141872
elevated expression of v-mos is correlated with altered differentiation of carcinoma cells.permanent alterations of the epithelial differentiation pattern were investigated after infection of hh-16 cl. 4 adenocarcinoma cells with moloney murine sarcoma virus (momusv). transformed cell clones with fibroblastoid morphology were isolated and compared with clones of unchanged epithelioid phenotype. southern blot analyses showed intact momusv proviral genomes in copy numbers between 4 and 9 in the dna of the morphologically transformed cell clones as well as in the clones with unaltered mo ...19902148370
the malignant histiocytosis sarcoma virus, a recombinant of harvey murine sarcoma virus and friend mink cell focus-forming virus, has acquired myeloid transformation specificity by alterations in the long terminal repeat.the malignant histiocytosis sarcoma virus (mhsv), in contrast to other viruses with the ras oncogene, induces acute histiocytosis in newborn and adult mice. molecular structure and function studies were initiated to determine the basis of its unique macrophage-transforming potential. characterization of the genomic structure showed that the virus evolved by recombination of the harvey murine sarcoma virus (ha-musv) and a virus of the friend-mink cell focus-forming virus family. structural analys ...19902152823
induction of transcription from the long terminal repeat of moloney murine sarcoma provirus by uv-irradiation, x-irradiation, and phorbol ester.the long terminal repeat (ltr) of moloney murine sarcoma virus (mo-musv) was used as a model system to study the stress response of mammalian cells to physical carcinogens. the chloramphenicol acetyltransferase (cat) gene was inserted between two mo-musv ltrs, and the ltr-cat-ltr construct was used for virus production and was integrated into the genome of nih 3t3 cells in the proviral form. this construct was used to assure that the integrated cat gene was driven by the promoter of the ltr. exp ...19902153296
reversion of thermosensitive splicing defect of moloney murine sarcoma virus ts110 by oversplicing of viral rna.moloney murine sarcoma virus ts110 possesses a thermosensitive splicing defect. by continuously growing nonproducer cells at the nonpermissive temperature, a new class of revertant cells, termed 6m3, that had lost the thermosensitive splicing defect was produced, and six distinct clones were selected. these cell clones were transformed at either permissive or restrictive temperatures. unlike parental 6m2 cells, which contain two virus-specific rna species of 4.0 and 3.5 kilobases (kb) at tempera ...19902154617
regulation of rna splicing in gag-deficient mutants of moloney murine sarcoma virus musvts110.we investigated whether the musvts110 gag gene product (p58gag) can regulate the novel growth temperature dependence of musvts110 rna splicing. musvts110 mutants with either frameshifts or deletions in the gag gene were tested for their ability to maintain the musvts110 splicing phenotype. only small decreases in splicing efficiency and no changes in the thermosensitivity of viral rna splicing were observed in musvts110 gag gene frameshift mutants. deletions within the gag gene, however, variabl ...19902157036
dna-binding proteins that interact with the long terminal repeat of radiation leukemia virus.we used the electrophoretic mobility shift assay to identify the interactions of nuclear proteins with the long terminal repeat of leukemogenic, thymotropic bl/vl3 radiation leukemia virus (radlv). in the promoter region, we identified a ccaat box-binding protein (cbp) that has the same binding characteristics as the ccaat box-binding protein that binds to the moloney murine sarcoma virus promoter and most likely represents the cp1 factor. in the upstream enhancer region unique to bl/vl3, we det ...19902157044
isolation and characterization of kirsten murine sarcoma virus-transformed mouse keratinocytes resistant to transforming growth factor beta.balb/mk (mk) is a continuous murine keratinocyte line whose cells are strictly dependent on exogenous epidermal growth factor (egf) for growth in culture. a derivative cell, kc, resulted from kirsten murine sarcoma virus transformation, and these cells no longer require egf for their growth. despite differences in mk and kc growth conditions, both cell lines are growth inhibited by picomolar concentrations of transforming growth factor-beta (tgf-beta). when mk and kc cells were maintained in the ...19902157456
suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.the acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [pmea; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of moloney murine sarcoma virus-induced tumor formation in mice. in the latter system pmea has stronger antiretroviral potency and selectivity than 3'-azido-3'-thymidine (azt). we have now investigated the effect of the drug in cats infected with the feline immunod ...19902158102
moloney murine sarcoma virus 349 induces kaposi's sarcomalike lesions in balb/c mice.moloney murine sarcoma virus (momusv349) is produced by musv349 cells in at least eight-fold excess over the replication-competent helper virus. less than 48-hours-old balb/c mice inoculated intraperitoneally with supernatant from musv349 cells containing approximately 10(4) musv349 infectious units developed clinical symptoms, including severe generalized wasting, 15 to 20 days after inoculation. these infected mice became moribund 35 to 45 days after inoculation. gross examination of the bodie ...19902158239
altered glycosylation in madin-darby canine kidney (mdck) cells after transformation by murine sarcoma virus.the changes in glycosylation of an immortalized epithelial cell line (mdck) before and after progression towards a more malignant phenotype have been studied. the parental mdck-3 cells were immortalized after long-term passage in vitro and have shown no tendency for spontaneous acquisition of malignancy-related phenotypes such as tumorigenicity, invasion and metastasis. they conserved morphological and functional characteristics of the epithelial tissue of origin. the ras-mdck cells acquired the ...19902158405
transcriptional activation of the adenine phosphoribosyltransferase promoter by an upstream butyrate-induced moloney murine sarcoma virus enhancer-promoter element.it has been documented that the activity of a specific promoter can be occluded by the presence of another promoter element upstream. we present evidence for a phenomenon contradictory to that predicted by the promoter occlusion theory. transcription from the hamster aprt (adenine phosphoribosyltransferase) promoter was augmented instead of repressed in transfected mouse l cells when an upstream moloney murine sarcoma virus enhancer-promoter element was induced with butyrate. without an adjacent ...19902159551
v-mos protein produced by in vitro translation has protein kinase activity.the v-mos protein, termed p37v-mos, has a closely associated serine/threonine protein kinase activity. to provide further information about its protein kinase activity, we tested the activity of p37v-mos produced in a cell-free translation system from transcripts generated from a cloned v-mos gene. anti-mos(37-55) immunoprecipitates of in vitro-produced p37v-mos were found to possess serine/threonine protein kinase activity, whereas those obtained with anti-mos(260-271), known to block v-mos aut ...19902159564
sequence-specific dna binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the moloney murine sarcoma virus.the ets proto-oncogene family is a group of sequence-related genes whose normal cellular function is unknown. in a study of cellular proteins involved in the transcriptional regulation of murine retroviruses in t lymphocytes, we have discovered that a member of the ets gene family encodes a sequence-specific dna-binding protein. a mouse ets-1 cdna clone was obtained by screening a mouse thymus cdna expression library with a double-stranded oligonucleotide probe representing 20 bp of the moloney ...19902163347
adhesion of kirsten-ras+ tumor-progressing and kirsten-ras- revertant 3t3 cells on fibronectin proteolytic fragments.adhesion has been evaluated for tumor cell populations derived from kirsten murine sarcoma virus (kimsv)-transformed balb/c 3t3 cells responding to substrata coated with intact plasma fibronectin (pfn), a family of related proteolytic fragments from pfn or cellular fibronectins (fns), and the heparan sulfate-binding platelet factor-4 (pf4). both early-passage kimsv cells, harboring the viral kirsten ras oncogene (v-ki-ras+), and late-passage kimsv cells, in which most cells have lost the oncogen ...19902163749
differences in targeting and secretion of cathepsins b and l by balb/3t3 fibroblasts and moloney murine sarcoma virus-transformed balb/3t3 fibroblasts.balb/3t3 fibroblasts (3t3) were observed to secrete latent, pepsin-activatable forms of cathepsin b and cathepsin l as well as an active form of beta-glucuronidase when cultured in the absence of serum. the secretion of these proteins was stimulated by the cation ionophore monensin: cathepsin b, 4.3-fold; cathepsin l, 7.2-fold; and beta-glucuronidase, 3.1-fold. these increases were accompanied by a 50% decline in cellular levels of the active forms of these enzymes and by the cellular accumulati ...19902166039
evidence for the multistep nature of in vitro human epithelial cell carcinogenesis.in keeping with the multistep development of human cancer in vivo, a stepwise approach to neoplastic transformation in vitro presents a reasonable strategy. we have recently developed an in vitro multistep model suitable for the study of human epithelial cell carcinogenesis. upon infection with the adenovirus 12-simian virus 40 hybrid virus, primary human epidermal keratinocytes acquired an indefinite life span in culture but did not undergo malignant conversion. subsequent addition of kirsten m ...19902167163
induction of moloney murine sarcoma virus tolerance in adult mice by anti-cd4 monoclonal antibody treatment.the role of cd4+ cells in the immune response to moloney murine sarcoma/leukemia virus complex was studied in adult mice undergoing long-term cd4+ cell functional depletion by treatment with anti-cd4 h129.19 monoclonal antibody (immunoglobulin g2a, kappa). adult mice given injections of moloney murine sarcoma/leukemia virus complex 1 day or 2 wk after monoclonal antibody treatment died with progressing sarcomas at the inoculation site; mice challenged 4 wk after such treatment, when cd4+ cells r ...19902167167
evidence for involvement of the protein kinase c pathway in the activation of p37v-mos protein kinase.protein kinases are known to undergo phosphorylation to regulate their activity. to determine whether the protein kinase activity of p37v-mos was similarly regulated, we investigated the influence of two well known protein kinases, namely protein kinase c and protein kinase a, on the activity of p37v-mos in vivo. nih3t3 cells chronically transformed with moloney murine sarcoma virus 124 were treated with high concentrations (200-400 nm) of phorbol 12-myristate 13-acetate (pma) for 24-48 h, conce ...19902168030
activation of cryptic splice sites in murine sarcoma virus-124 mutants.we have examined splice site activation in relation to intron structure in murine sarcoma virus (musv)-124 rna. musv-124 contains inactive murine leukemia virus env gene splice sites (termed 5' env and 3' env) as well as cryptic sites in the gag and v-mos genes (termed 5' gag and 3' mos) which are activated for thermosensitive splicing by a 1,487-base intronic deletion in the musv-124 derived musvts110 retrovirus. to determine conditions permissive for splice site activation, we examined musv-12 ...19902170671
revertants of v-fos-transformed rat fibroblasts: suppression of transformation is dominant.phenotypic revertants of finkel-biskis-riley (fbr)-murine sarcoma virus-transformed rat fibroblasts were isolated on the basis of their adherence to plastic tissue culture dishes in the absence of divalent cations. some revertants had sustained deletions or inactivating mutations of the v-fos gene. however, two revertants expressed a functional v-fos gene at levels equal to that in the transformed parental cells, and therefore phenotypic reversion was due to mutations in nonviral genes. these re ...19902172782
v-k-ras transformation induces reversion to an earlier developmental form in adult rat adrenal cells.the basis for specific changes in differentiation that accompany ras-oncogene-mediated transformation are not understood. when short-term cultures of fibroblast-like cells from adult rat adrenal glands were transformed with kirsten murine sarcoma virus (kimsv), the original stromal characteristics of the target cells (metachromatic extracellular matrix, high collagen production, collagen incorporation into pericellular matrix and a fibroblastic morphology and growth pattern) diminished. in contr ...19902194873
s-antigen: from gene to autoimmune uveitis.retinal s-antigen (s-ag) is capable of inducing experimental autoimmune uveitis (eau) in laboratory animals. eau may serve as an animal model for studying human uveitis. as a first step we have determined the nucleotide sequence of an s-ag gene and its cdnas. the amino acid sequences were deduced from the cdnas of various animals and human. four uveitopathogenic sites in bovine s-ag were characterized. one of the sites (peptide m) has sequence homology with non-self proteins from baker's yeast, ...19902197111
histologic variation among experimental tumors of common origin: relationships to viral p21 expression and to tumor-derived extracellular matrix.transformed lines, obtained by infection of adult rat adrenocortical fibroblast-like cells with kirsten murine sarcoma virus, produce s.c. tumors which range histologically from fibrosarcomas to carcinomas to undifferentiated neoplasms. this study was undertaken to determine whether the histology was a stable characteristic of individual lines and whether it was related to oncogene expression and to differentiation in culture. three lines were infected at passage 1 and tumor histology, different ...19902210883
malignant transformation of an infinite life span human fibroblast cell strain by transfection with v-ki-ras.to determine if human fibroblasts can be transformed into malignant cells by transfection of a k-ras oncogene, we transfected the provirus of kirsten murine sarcoma virus (v-ki-ras) into an infinite life span human cell strain, msu-1.1, which has a normal morphology, is not anchorage independent, and has a stable, near-diploid karyotype. the transfected populations gave rise to distinct foci composed of morphologically-altered cells. the cells from several independent foci were isolated, propaga ...19902216465
transformation by v-h-ras does not restore proliferation of a set of temperature-sensitive cell-cycle mutants of rat 3y1 fibroblasts.three temperature-sensitive cell-cycle mutants of rat 3y1 fibroblasts (3y1tsd123, 3y1tsg125, and 3y1tsh203, each belonging to distinct complementation groups) were transformed with plasmid dna carrying harvey murine sarcoma virus cdna. the criteria for transformation were increase in saturation cell density, capability to clone in soft agar, and alteration in the cellular morphology. at 39.8 degrees c (restrictive temperature of the parental cell lines), all the transformed sublines of each muta ...19902257639
inhibitory effects of 9-(2-phosphonylmethoxyethyl)adenine and 3'-azido-2',3'-dideoxythymidine on tumor development in mice inoculated intracerebrally with moloney murine sarcoma virus.9-(2-phosphonylmethoxyethyl)adenine (pmea), a potent inhibitor of human immunodeficiency virus (hiv), caused a dose-dependent suppression of tumor formation, and mortality associated therewith, in 6-day-old nmri mice inoculated intracerebrally with moloney murine sarcoma virus (msv). even at a dose as low as 1 mg/kg/day, pmea effected a significant delay in tumor formation. when evaluated in parallel with pmea, 3'-azido-2',3'-dideoxythymidine (azt) conferred a comparable tumor-inhibitory effect ...19902307539
reversibility of the antiproliferative effect of interferon.the reversibility of the antiproliferative effect of interferon (ifn) and its correlations to the induction of (2',5') oligoadenylate synthetase (2-5a synthetase) activity was studied on nih/3t3 cells transformed by moloney murine sarcoma virus. the cells were treated with various doses of mouse beta-ifn. at 72 h after treatment, the cultures were subdivided. while half received fresh doses of ifn, the second half received no ifn. reversibility of the ifn effect was then followed. three differen ...19902370879
anti-retrovirus activity of 9-(2-phosphonylmethoxyethyl)adenine (pmea) in vivo increases when it is less frequently administered.different treatment schedules have been investigated when evaluating the inhibitory effect of 9-(2-phosphonylmethoxyethyl)adenine (pmea) and 3'-azido-2',3'-dideoxythymidine (azt) on the replication of human immunodeficiency virus type i (hiv-i) in mt-4 cells, transformation of c3h/3t3 cells by moloney murine sarcoma virus (msv), and msv-induced tumor formation in newborn nmri mice. shortening the exposure time of hiv-i-infected mt-4 cells to pmea or azt led to an increase in the selectivity inde ...19902384280
extinction and activation of the thyroglobulin promoter in hybrids of differentiated and transformed thyroid cells.thyroglobulin gene expression was repressed in a rat thyroid cell line transformed with kirsten murine sarcoma virus. expression of a dominant selectable marker driven by the thyroglobulin promoter was also inhibited. somatic cell hybridization of transformed and differentiated thyroid cells resulted in extinction of thyroglobulin gene expression. when transformed cells carrying a dominant selectable marker driven by the thyroglobulin promoter were fused to differentiated cells and expression of ...19902406559
keratin expression of both chemically and virally transformed human epidermal keratinocytes during the process of neoplastic conversion.human epidermal cells, despite being 'immortalized' or 'transformed' by combinations of either oncogenic virus (sv40, adenovirus 12 or kirsten murine sarcoma virus) or chemical carcinogen (n-methyl-n'-nitro-n-nitrosoguanidine or 4-nitroquinoline-1-oxide) exhibited similar keratins (although quantitatively reduced) to that of control cells when grown in vitro. however, athymic nude mouse tumors derived from such cells exhibited suppression of the 52, 56 and 58 kd (basic type ii) keratins and a pr ...19862417737
class ii histocompatibility antigen expression in human melanocytes transformed by harvey murine sarcoma virus (ha-msv) and kirsten msv retroviruses.human melanocytes infected with ki-msv or ha-msv, but not amphotropic mulv, undergo a series of transformation-related changes that are characteristic of malignant melanoma. these are (a) expression of ia antigens, in particular dp, dq, and dr class ii histocompatibility gene products, (b) a transformed morphology and ability to grow in soft agar, and (c) a 5-10-fold increase in the cell surface expression of gd3 ganglioside. however, other characteristics of melanoma, such as independence from ...19862430046
an activated harvey ras oncogene produces benign tumours on mouse epidermal tissue.studies of the mutagenic action required for specific chemicals to produce benign or malignant tumours suggest that in mouse skin at least two genetic events occur before carcinoma formation. the isolation of an activated form of the c-rash gene from skin papillomas has provided evidence that this gene may be a target for the first mutation, which could constitute the initiating mutation in skin carcinogenesis. in vitro studies indicate that the v-rash gene of harvey murine sarcoma virus (ha-msv ...19862430189
a syngeneic monoclonal antibody to murine meth-a sarcoma (hepss-1) recognizes heparan sulfate glycosaminoglycan (hs-gag): cell density and transformation dependent alteration in cell surface hs-gag defined by hepss-1.we have isolated a syngeneic monoclonal antibody (hepss-1) reactive to a murine methylcholanthrene-induced fibrosarcoma, meth-a. hepss-1 also bound to a wide variety of established and fresh normal cells derived from not only mice but also other species such as human, monkey, rat, hamster, and chicken. immunoprecipitation of surface iodinated meth-a cell extract with hepss-1, as well as sepharose 4b gel chromatography of meth-a cell extract and detection of antigens recognized by hepss-1 by a sa ...19862431047
enhanced g2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture.a deficiency in dna repair, manifest as enhanced chromatid radiosensitivity during the g2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. normal epidermal keratinocytes established as continuous cell lines by transfection with psv3-neo or infection with adeno 12-sv40 hybrid virus developed enhanced g2 chromatid radiosensitivity a ...19872434215
expression of the c-raf protooncogene in human hematopoietic cells and cell lines.the murine sarcoma virus 3611 contains the transforming v-raf gene that has partial nucleotide homology with the src family of tyrosine kinase-encoding oncogenes. although this virus induces fibrosarcomas in mice, a recombinant murine retrovirus carrying both the raf and myc oncogenes induces immunoblastic lymphomas and immortalizes mouse macrophages in vitro. the present study has thus monitored the expression of c-raf in human hematopoietic cells. the results demonstrate the presence of a 3.6- ...19872436688
temporary inhibition of moloney-murine sarcoma virus (m-msv) induced-tumours by adoptive transfer of ricin-treated t-lymphocytes.the potential use of tumour-specific t-lymphocytes loaded with ricin in cell targeting experiments was investigated. moloney-murine sarcoma virus (m-msv)-specific t-lymphocytes, obtained in mass mixed leucocyte-tumour cell culture (mltc) and a m-msv-specific cytotoxic t-lymphocyte (ctl) clone, were incubated with 125i-labelled ricin in order to evaluate toxin uptake and release. the internalized ricin (4.5 x 10(-17) mol and 6.5 x 10(-17) mol per 10(2) mltc and ctl clone cells, respectively) was ...19872437947
characterization of hyaluronate binding proteins isolated from 3t3 and murine sarcoma virus transformed 3t3 cells.a hyaluronic acid binding fraction was purified from the supernatant media of both 3t3 and murine sarcoma virus (msv) transformed 3t3 cultures by hyaluronate and immunoaffinity chromatography. sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (mr,e) 70k, 66k, and 56k which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (habp). hyaluro ...19872440472
murine retroviruses control class i major histocompatibility antigen gene expression via a trans effect at the transcriptional level.moloney murine leukemia virus (m-mulv) and moloney murine sarcoma virus (m-msv) exert a regulatory effect on the class i genes of the murine major histocompatibility complex (mhc). we have previously shown that m-mulv infection of mouse fibroblasts results in a substantial increase in cell surface expression of h-2k, h-2d, and h-2l proteins, whereas m-msv, upon coinfection of the same cells, is apparently able to override the mulv-induced increase in h-2 expression. as a result of this modulatio ...19872441241
changes in cellular gene expression in rat thyroid epithelial cells transformed by the kirsten murine sarcoma virus.we have exploited a recently characterized system of rat thyroid epithelial cells transformed by the wild-type (wt) and a temperature-sensitive (ts) mutant strain of the kirsten murine sarcoma virus (ki-msv) in order to study the effects of the k-ras oncogene on the gene expression of differentiated thyroid epithelial cells. by using cdnas isolated from normal thyroid glands as probes, we were able to identify three sets of cellular sequences whose expression is influenced by the v-k-ras oncogen ...19872442021
nuclear transport in 3t3 fibroblasts: effects of growth factors, transformation, and cell shape.nucleocytoplasmic transport of fluorescent-labeled macromolecules was investigated in transformed and nontransformed 3t3 fibroblasts. insulin and epidermal growth factor enhanced transport three-fold after 1-2-h incubation with nontransformed adhering fibroblasts; no enhancement of transport was observed for spherical unattached fibroblasts. the concentration of growth factor for maximal enhancement was 3-10 nm. nuclear transport for kirsten murine sarcoma virus-transformed balb/c 3t3 fibroblast ...19882448310
antibodies against viral proteins can be produced effectively in response to the increased uptake of alpha 2-macroglobulin:viral protein conjugate by macrophages.we have previously shown that foreign antigens conjugated to alpha 2-macroglobulin (alpha 2m) were effectively taken up by macrophages, which was followed by a remarkable increase in the proliferation of immune t cells. we present in this report that the production of antibodies against viral proteins can also be effectively achieved when viral proteins were conjugated to alpha 2m and fed to the in vitro immune system. proteins derived from kirstein murine sarcoma virus (ki-msv) were partially p ...19882449204
5-azacytidine inhibits adipocytic conversion of human skin fibroblasts by kirsten murine sarcoma virus and dexamethasone.transformation of human skin fibroblasts (sf) by the kirsten murine sarcoma virus (kimsv) is associated with their neodifferentiation into preadipose cells. hydrocortisone or dexamethasone (dx) promote the transformation/neodifferentiation of preadipocytes to fully differentiated adipocytes. 5-azacytidine (5-aza-cr) by itself, or together with dx, or immediately after inoculation with kimsv did not cause adipocytic conversion of human sf. addition of 5-aza-cr either before or immediately after e ...19872450793
alpha, beta- and beta, gamma-methylene 5'-phosphonate derivatives of 3'-azido-2',3'-dideoxythymidine-5'-triphosphate. correlation between affinity for reverse transcriptase, susceptibility to hydrolysis by phosphodiesterases and anti-retrovirus activity.a series of 5'-phosphorylated derivatives of 3'-azido-2',3'-dideoxythymidine (azddthd), including azddthd 5'-mono- and 5'-triphosphate, alpha, beta-methylene azddthd-5'-diphosphate, alpha,beta-methylene azddthd-5'-triphosphate, and beta,gamma-methylene azddthd-5'-triphosphate, were evaluated for their cytostatic and anti-retrovirus properties, and their inhibitory effects on the reverse transcriptases of moloney murine leukemia virus and human immunodeficiency virus. in contrast with the 5'-mono ...19882455521
immortalization of murine connective tissue-type mast cells at multiple stages of their differentiation by coculture of splenocytes with fibroblasts that produce kirsten sarcoma virus.mature connective tissue mast cells (ctmc) have not been previously available as a cell line from any species. here we describe 15 novel mast cell lines (kisv-mc) that were derived by coculturing murine splenocytes with fibroblasts that produce a ki-ras-containing murine sarcoma virus. some of the kisv-mc lines are similar to ctmc in that they synthesize predominantly heparin proteoglycans, and contain up to 35 micrograms of histamine and 2.2 units of carboxypeptidase a/10(6) cells in secretory ...19882457591
alteration of growth and differentiation factors response by kirsten and harvey sarcoma viruses in the il-3-dependent murine hematopoietic cell line 32d c13(g).32d c13(g) is an interleukin 3(il3)-dependent non-tumorigenic murine hematopoietic cell line which undergoes terminal differentiation into granulocytes when exposed to granulocytic colony stimulating factor (g-csf). infections of 32d c13(g) cells with either kirsten rat sarcoma virus or balb murine sarcoma virus, both containing a v-ras oncogene, generates clones that can permanently grow in g-csf without differentiation. 32d-ki-ras cells show a heterogeneous morphology ranging from the promyelo ...19892468124
reactivation of thyroglobulin gene expression in transformed thyroid cells by 5-azacytidine.transformed rat thyroid cells fail to express thyroglobulin. cells transformed with a kirsten murine sarcoma virus carrying a temperature-sensitive ras allele lose their transformation phenotype when shifted to the nonpermissive (39 degrees c) temperature. the thyroglobulin promoter, however, remains inactive. similarly, transfection of these cells with a thyroglobulin promoter fused to a neomycin resistance reporter gene does not produce clones resistant to g418. treatment of the transfected ce ...19892476239
combined treatment with pseudomonas aeruginosa toxin and interferon on mouse and human cells.the combined biological effect of pseudomonas toxin and beta-interferon on mammalian cells was studied on two cell lines. the first was a virus-producing clone derived from nih/3t3 mouse fibroblasts transformed by moloney murine sarcoma virus. the second was a clone derived from human amnion cells. the parameters examined were either retrovirus release from the mouse cells or the rate of protein synthesis in both cell lines. when applied together with pseudomonas toxin, interferon inhibits virus ...19892476872
5-azacytidine-induced recovery of o6-alkylguanine--dna alkyltransferase activity in mouse ha821 cells.mouse ha821 cells, harvey murine sarcoma virus-transformed nih3t3 cells, have extremely low o6-alkylguanine--dna alkyltransferase (o6agtase) activity and are hypersensitive to an anti-tumor chloroethylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (acnu). the treatment of ha821 cells with a dna demethylating agent, 5-azacytidine, resulted in an increase in the frequency of acnu-resistant cell clones. all randomly isolated acnu-resistant cell c ...19892477166
abolishment of c-fos inducibility in ras-transformed mouse osteoblast cell lines.proto-oncogene c-fos is induced by many types of cellular stimuli, such as 12-o-tetradecanoylphorbol-13-acetate (tpa), epidermal growth factor (egf), serum (fetal bovine), calcium ionophore a23187, and dibutyryl camp (but2camp). in this study, c-fos induction was abolished in ras-transformed mouse osteoblast cells (mc3t3). transformants of mc3t3 were isolated after transfection with ki or ha murine sarcoma virus dna. all ki- or ha-ras transformed mc3t3 clones examined showed exceedingly low leve ...19892478147
a cell mutant that exhibits temperature-dependent sensitivity to transformation by various oncogenes.we previously isolated a fisher rat fibroblast mutant, b812, that has the unique property of temperature-dependent transformation by various oncogenic retroviruses. at the permissive temperature (35 degrees c), this mutant was sensitive to oncogenic transformation and formed foci on a dish at the same frequency as did the parental fibroblast cell line. when kirsten murine sarcoma virus (ki-msv) was applied to the cells, the frequency of focus formation decreased more than 25-fold at the nonpermi ...19892479832
expression of nf-l and nf-m in fibroblasts reveals coassembly of neurofilament and vimentin subunits.we have used transient and stable dna transfection to force synthesis of the mouse nf-l and nf-m genes in nonneuronal cultured animal cells. when the authentic nf-l gene (containing 1.7 kb of sequences 5' to the transcription initiation site) was transfected into l cells, correctly initiated nf-l mrna was produced from the transfected gene but not the endogenous nf-l genes. therefore, the normal restriction of nf-l expression to neurons cannot derive exclusively from absence in nonneuronal cells ...19892493000
interaction of v-ki-ras oncogene and interferon-gamma in the control of histocompatibility antigen expression in mouse fibroblasts.c3h10t1/2 fibroblasts when transformed with kirsten murine sarcoma virus lose the ability to be induced to express class ii major histocompatibility complex antigens when induced with interferon-gamma (ifn-gamma). sublines were derived from transformed lines by cell sorting after treatment with ifn-gamma, sorting for low or high expression of h-2ak. these sublines remained stably noninducible or inducible for class ii antigen for several passages after sorting. in all other respects tested, viz, ...19892497992
instability of expression of major histocompatibility antigens in fibroblasts expressing activated ras oncogene: constitutive and interferon-gamma induced class i and class ii antigens in a series of clonal isolates of murine fibroblasts transformed by v-ki-ras.we have examined the expression of major histocompatibility complex (mhc) antigens, constitutive or induced with interferon gamma (ifn-gamma), in a line of c3h mouse embryo fibroblasts (c3h 201) transformed with a helper-virus-free preparation of the kirsten strain of murine sarcoma virus. c3h 201 cells expressed some class i antigen (h-2kk) in the absence of added interferon, unlike the parental c3h 10t1/2 cells from which they were derived. however, this declined with (in vitro) passage level ...19892504267
transformed cells overexpress a cytosolic nucleic acid binding protein.a protein blotting technique was used to identify a 57,000 dalton cytosolic nucleic-acid-binding protein found in neoplastically transformed cell lines. specifically, greater amounts of this protein were found in kirsten murine sarcoma virus-, simian virus 40-, and methylcholanthrene-transformed balb 3t3 cells than in comparable untransformed cells. an analogous protein was identified in other transformed mammalian cells. increased levels of the dna binding protein in sarcoma virus transformants ...19892506192
changes in integrin receptors on oncogenically transformed cells.oncogenically transformed cells show reduced assembly of fibronectin-rich extracellular matrixes and diminished ability to adhere to fibronectin. the molecular bases of these phenotypic alteration are not fully understood. we report here alterations in the spectrum of integrins, including two fibronectin receptors, on oncogenic transformation of rodent cells. transformation of rat1, nrk, and nil8 cells by rous sarcoma virus or by murine sarcoma viruses encoding ras oncogenes leads to reductions ...19892521461
presence of a constitutive paracrine beta-interferon in v-mos-bearing nonmalignant reverted cells.a stable nonmalignant revertant cell line was derived from moloney murine sarcoma virus-transformed balb/c cells after long-term cultivation in the presence of murine type i interferon (ifn). these cells gradually established resistance to exogenous ifn and were also seen to contain ifn-dependent proteins. the presence of an endogenous ifn was confirmed by the results of northern blot analysis and in situ hybridization with an ifn-beta probe, showing that only mrna specific for ifn-beta- could b ...19892521813
a mechanism of c-raf-1 activation: fusion of the lipocortin ii amino-terminal sequence with the c-raf-1 kinase domain.in order to understand the mechanism of oncogenic activation, we have analyzed the c-raf-1 gene from the gl-5-jck human glioblastoma, which underwent rearrangement during transfection experiments. nucleotide sequencing of cdna clones derived from the 2.5 kb raf-mrna, which is a major transcript of raf in nih3t3 cells transformed with gl-5-jck dna, revealed that this mrna contains sequences derived from the human c-raf-1 gene and the human lipocortin ii gene. translation of the 2.5 kb raf-mrna pr ...19892524024
a rat mutant cell clone showing temperature-dependent transformed phenotypes with functional expression of the src gene product.the cellular mutant b814 isolated from a fischer rat cell line shows temperature-sensitivity of focus formation on infection with moloney murine sarcoma virus (mo-msv) and rous sarcoma virus (rsv). an rsv-transformed clone (s814-2) isolated from b814 cells shows temperature-sensitive transformed phenotypes for morphology, growth in soft agar, and glucose uptake. the expression, phosphorylation, and tyrosine kinase activity of pp60v-src in s814-2 were not affected at the nonpermissive temperature ...19892535907
induction of effective immunity to moloney murine sarcoma virus using monoclonal anti-idiotypic antibody as immunogen.we have isolated an anti-idiotypic mab (rs1.1.3), which recognizes an idiotope present on several igm mab specific for moloney murine leukemia virus (m-mulv)-determined cell surface ag. the binding of rs1.1.3 to idiotypic antibody could be inhibited by specific ag. intraperitoneal immunization of mice with purified rs1.1.3 antibody-induced effective immunity against moloney murine sarcoma virus challenge. a single injection of rs1.1.3 7 days before virus challenge resulted in a 27% reduction in ...19892536772
2'-5'-oligoadenylate synthetase gene expression in normal and murine sarcoma virus-transformed nih 3t3 cells.mouse fibroblasts transformed by murine sarcoma virus (msv) are highly sensitive to the antiproliferative effect of interferon (ifn) (m. bakhanashvili, d. h. wreschner, and s. salzberg, cancer res. 43:1289-1294, 1983). to elucidate the mechanism leading to this ifn sensitivity, the expression of the 2'-5'-oligoadenylate synthetase (2-5a synthetase) gene, the presence of the 2-5a synthetase protein, and the level of its enzymatic activity were determined in ifn-treated and untreated cultures. nih ...19892536824
harvey murine sarcoma virus: influences of coding and noncoding sequences on cell transformation in vitro and oncogenicity in vivo.the rat-derived harvey murine sarcoma virus (ha-musv) contains a transduced ras oncogene activated by two missense mutations and flanked by rat retroviruslike vl30 sequences. ha-musv induces focal transformation of mouse nih 3t3 cells in vitro and tumors (fibrosarcomas and splenic erythroleukemias) in newborn mice. we have used these two assays to study the contribution of coding and noncoding viral sequences to the biological activity of ha-musv. a good correlation was found between the in vitr ...19892536840
secretion, glycosylation, and phosphorylation of rat-specific, transformation-associated proteins in moloney murine sarcoma virus-transformed rat cells.previously, we detected, by monoclonal antibody, three moloney murine sarcoma virus (mo-msv)-activated intracellular transformation-associated proteins (tap), (p66, p63, and p60) in several mo-msv-transformed rat cell lines (chan et al., biochem. biophys. res. commun., 134: 1223-1230, 1986) and found the release of tap into the extracellular medium with a change from three intracellular polypeptides to two extracellular polypeptides (p68 and p64) (li et al., virology, 156: 91-100, 1987). since t ...19892538234
the kirsten murine sarcoma virus induces rat thyroid carcinomas in vivo.the injection of a retrovirus carrying the v-ras-ki oncogene into the thyroid gland of adult fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. more than one hundred adult fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the kirsten murine sarcoma virus (kimsv). within three months m ...19892538791
differential patterns of intracellular metabolism of 2',3'-didehydro-2',3'-dideoxythymidine and 3'-azido-2',3'-dideoxythymidine, two potent anti-human immunodeficiency virus compounds.3'-azido-2',3'-dideoxythymidine (azt) and 2',3'-didehydro-2',3'-dideoxythymidine (d4t) are potent and selective inhibitors of human immunodeficiency virus replication in mt-4 and ath8 cells. they are also inhibitory to the replication of murine retroviruses, i.e. moloney murine sarcoma virus-induced transformation of c3h cells. in mt-4 cells azt is readily phosphorylated to its 5'-monophosphate, while the 5'-di- and 5'-triphosphates are generated to a 200-600-fold lower extent than the 5'-monoph ...19892539371
regulation of ifn-gamma-induced host cell mhc antigen expression by kirsten msv and mlv. i. effects on class i antigen expression.we have reported previously that the kirsten murine sarcoma virus (ki-msv) that carries the v-ki-ras oncogene prevents c3h10t 1/2 fibroblasts from being able to respond to interferon-gamma (ifn-gamma) with the expression of the class ii major histocompatibility complex (mhc) antigen, h-2a. in this report we investigate further as to whether msv or its parent virus kirsten murine leukaemia virus (ki-mlv) is able to reduce host class i mhc antigen expression. the results demonstrate that class i e ...19892544513
regulation of ifn-gamma-induced host cell mhc antigen expression by kirsten msv and mlv. ii. effects on class ii antigen expression.we have reported previously that the kirsten murine sarcoma virus (ki-msv), which carries the v-ki-ras oncogene, prevents the induction of the class ii mhc antigen h-2a and reduces the induction of class i mhc antigens by interferon-gamma (ifn-gamma) on c3h10t 1/2 fibroblasts. it is here shown that the abolition by the virus of h-2a expression extends also to class ii antigen h-2e and that this is maintained for at least 7 days after ifn treatment. in addition no concentration of ifn-gamma teste ...19892544514
potentiating effect of ribavirin on the anti-retrovirus activity of 3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside in vitro and in vivo.3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside (azdddapr) is a potent and selective inhibitor of human immunodeficiency virus (hiv) replication in vitro. it also inhibits moloney murine sarcoma virus (msv)-induced transformation of murine c3h/3t3 embryo fibroblasts. azdddapr causes a marked dose-dependent suppression of msv-induced tumor formation and mortality therewith associated in newborn mice infected with msv. combination of azdddapr with ribavirin resulted in a marked potentiation of it ...19892545163
c-fos expression induces bone tumors in transgenic mice.the proto-oncogene c-fos has been isolated as the cellular homolog of the v-fos gene found in the osteosarcoma inducing fbr- and fbj-murine sarcoma viruses (msv). expression of the c-fos gene in transgenic mice leads to the development of bone lesions of which about half progress to bone tumors mainly chondrosarcomas. the tumors display a strong preference for males and have a latency with a mean of 9.5 months. however, also mice without visible lesions develop bone tumors with the same sex pref ...19892547184
oncogenicity of human n-ras oncogene and proto-oncogene introduced into retroviral vectors.the n-ras gene is the only member of the ras family which has never been naturally transduced into a retrovirus. in order to study the in vitro and in vivo oncogenicity of n-ras and to compare its pathogenicity to that of h-ras, we have inserted an activated or a normal form of human n-ras cdna into a slightly modified harvey murine sarcoma virus-derived vector in which the h-ras p21 coding region had been deleted. the resulting constructions were transfected into nih 3t3 cells. the activated n- ...19892548008
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