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molecular cloning of the mason-pfizer monkey virus genome: biological characterization of genome length clones and molecular comparisons to other retroviruses.the molecular cloning of the dna provirus of mason-pfizer monkey virus (m-pmv) is described. fourteen independent clones of integrated m-pmv proviruses were isolated from a human embryo kidney cell line that had been previously derived from a single cell clone infected with m-pmv. characterization of these clones for size of insert, restriction pattern of flanking dna, and presence of repetitive dna in the flanking sequences revealed that 10 of the isolates were identical while the four remainin ...19863016990
highly sensitive immunoadsorption procedure for detection of low-abundance proteins.a procedure that virtually eliminates nonspecific adsorption of radiolabeled proteins during immunoprecipitation was devised utilizing staphylococcal cells containing protein a (staph a). immunoprecipitates (antigen-antibody complexes) were solubilized from staph a pellets into detergent micelles by incubation in a small volume of 1% sodium dodecyl sulfate (sds) at 23 degrees c for 10 min. to allow re-formation of immunocomplexes and rebinding to new staph a, the sds-solubilized material was dil ...19863017145
hormone dependence and independence of mammary tumors in mice. 19863017886
stoichiometric analysis of the specific interaction of the glucocorticoid receptor with dna.purified preparations of activated glucocorticoid x receptor complex (gr) contain a mr 94,000 hormone-binding polypeptide co-purifying together with a mr 72,000 non-hormone-binding polypeptide (wrange, o., okret, s., radojcic, m., carlstedt-duke, j., and gustafsson, j.-a. (1984) j. biol. chem. 259, 4534-4541). gr binds selectively to discrete regions of dna in mouse mammary tumor virus (payvar, f., defranco, d., firestone, g.l., edgar, b., wrange, o., okret, s., gustafsson, j.-a., and yamamoto, ...19863017946
tumor-specific idiotype vaccines. i. generation and characterization of internal image tumor antigen.the concept of idiotype vaccines against tumor-associated antigens (taa) was tested in the dba/2 l1210 lymphoma subline, l1210/gzl. monoclonal antibodies against a taa that cross-reacts with the envelope glycoprotein gp52 of the mammary tumor virus were used to make hybridoma anti-idiotype antibodies (ab2). in this report we describe the characterization of monoclonal anti-idiotypic antibodies against the combining site of 11c1 (ab1), which recognizes a shared determinant of gp52 of mouse mammar ...19863018080
exogenous mouse mammary tumor virus proviral dna isolated from a kidney adenocarcinoma cell line contains alterations in the u3 region of the long terminal repeat.mouse mammary tumor virus (mmtv) is a b-type retrovirus which induces predominantly mammary carcinomas after a relatively long latency period. to date, very little is known about the reasons for the strict tissue specificity of mmtv. the balb/cf/cd strain of mice, which was infected with milk-borne mmtv (c3h), shows a high incidence of kidney adenocarcinomas, and our data suggest that mmtv might be involved in the formation of these tumors. newly integrated exogenous mmtv proviruses were found i ...19863018276
interference of mouse mammary tumor virus replication by ptt.119 [p-fluoro-l-phe-m-bis-(2-chloroethyl)amino-l-phe-met ethoxy hcl]--an antitumor agent.ptt.119 [p-fluoro-l-phe-m-bis-(2-chloroethyl)-amino-l-phe-met ethoxy hcl] is a new bifunctional alkylating compound that possesses both cytolytic and antiviral activities. continuous treatment of mouse mammary tumor cells with 15 microm ptt.119 reduced production of the b-type retrovirus murine mammary tumor virus (mumtv). mumtv levels in ptt.119-treated cultures were reduced by 31% in the first 24 hours; an additional 24 hours of treatment resulted in a further reduction of 70%. these reduction ...19863005743
an endogenous mouse mammary tumor virus genome common in inbred mouse strains is located on chromosome 6.we have examined ecori-restricted cellular dna from mouse-hamster somatic cell hybrids. results of this analysis show that the unit ii mouse mammary tumor virus proviral genome is located on mouse chromosome 6. restriction analysis of cellular dna from (c3h/ouj x czech ii) x czech ii backcross mice showed a strong linkage between unit ii and igk. the gene order of these markers on chromosome 6 relative to the raf and kirsten murine sarcoma virus ras-2 proto-oncogenes was established.19863003402
construction of a retroviral cdna version of the int-1 mammary oncogene and its expression in vitro.the int-1 mammary oncogene is activated by proviruses of the mouse mammary tumor virus in many different mammary tumors. we have inserted a genomic fragment containing the protein-encoding domain of the gene into the retroviral shuttle vector pzipneosv(x)1. after one round of virus replication we recovered recombinant proviral dna containing a correctly spliced copy of int-1. in vitro transcription of this cdna version of int-1 using sp6 polymerase and translation in a reticulocyte lysate yielde ...19863003692
a complete library of point substitution mutations in the glucocorticoid response element of mouse mammary tumor virus.the glucocorticoid response element (gre) of mouse mammary tumor virus (mmtv) was chemically synthesized as two complementary dna strands bearing cohesive termini. during automated synthesis, random mutations were introduced into the dna by "doping" each of the four nucleoside phosphoramidites (a, g, c, and t) with a low level of the other three. these preparations were annealed and cloned into an m13 phage vector to produce a library of gre mutants. mutations within the synthesized region were ...19863003746
cyclic amp suppresses expression of v-rash oncogene linked to the mouse mammary tumor virus promoter.clone 433.3 of nih 3t3 cells is a stable carrier of the mmtv ltr:v-rash chimeric dna. only in the presence of dexamethasone (a synthetic glucocorticoid), 433.3 cells exhibit an induced level of p21 transforming protein and phenotypic transformation. n6,o2'-dibutyryl camp (dbcamp) antagonized the effect of dexamethasone in a time - and concentration - dependent manner. dbcamp (5 x 10(-4)m) added 18 hr prior to the addition of dexamethasone (10(-7)m) almost completely blocked the hormone effect: c ...19863004443
expression of retroviral sequences and oncogenes in murine hepatocellular tumors.the expression of endogenous retroviral sequences and of three cellular oncogenes was examined in three hepatocellular adenomas and in four carcinomas induced in male c57bl/6jdp x c3hf/dp f1 (hereafter called b6c3f1) mice by a single dose of nitrosodiethylamine, in five carcinomas that arose spontaneously in male c3hf mice, and in the livers of normal age-matched control mice. in all of these adenomas and carcinomas, there was increased expression of moloney murine leukemia virus- and intraciste ...19863004709
a new site of integration for mouse mammary tumor virus proviral dna common to balb/cf(c3h) mammary and kidney adenocarcinomas.the balb/cf/cd substrain of mice, developed by inbreeding and selection, shows a 70% incidence of spontaneous kidney adenocarcinomas. initially foster-nursed on c3h mothers, these mice no longer produce mammary tumors, but there is evidence that mouse mammary tumor virus (mmtv) is involved in the formation of these renal carcinomas. we identified a chromosomal region called int-41, representing a locus interrupted by the integration of an exogenous mmtv provirus in a balb/c mammary tumor. we fou ...19863007110
serologic responses to murine mammary tumor virus (mumtv) in mumtv-exposed laboratory personnel.a retrospective study was conducted to determine whether exposure to murine mammary tumor virus (mumtv) induced mumtv-specific serologic responses among intramural laboratory personnel. results obtained with a panel of five purified structural proteins of the riii mouse strain milk-derived mumtv (gp55, gp34, p28, p18, and p12), by means of the enzyme-linked immunosorbent assay to assess antibody binding, established that mumtv exposure resulted in highly significant increases in serologic respon ...19863007844
the effects of 2-deoxyglucose and tunicamycin on the biosynthesis of the murine mammary tumor virus proteins, and on the assembly and release of the virus.the role of glycosylation in the biosynthesis, processing, and shedding of the murine mammary tumor virus (mumtv) glycoproteins and in virus production was investigated in a clonal mammary tumor cell line, gr-3a, using two inhibitors of protein glycosylation, 2-deoxyglucose (2-dg) and tunicamycin (tm). it was found that both 2-dg and tm completely inhibited the synthesis of the mumtv envelope precursor polyprotein, pr70env, and, as a consequence, the synthesis of the viral glycoproteins gp52 and ...19863008416
immunohistochemical expression of mammary tumor virus antigens in mammary glands of virgin mice, in relation to mtv genes.mtv antigens in the resting mammary glands of grs/a, shn, c3h, and balb/c virgin mice were detected by immunoperoxidase techniques using antiserum against mtv whole virion, gp 52 or p 25 to differentiate the expression between endogenous and exogenous mtv. balb/c mice were crossed to infect mtv into each reciprocal hybrid or fosternursed inbred. immunohistochemical stainings of gp 52 in the formol-fixed sections were almost the same as those of the whole mtv virion, and the results on various ca ...19863008497
[identification of the nucleotide sequences specific for the 5'-flanking regions of the genes regulated by glucocorticoids by a computer analysis method].nucleotide sequences of 5'-flanking regions of 11 glucocorticoid-regulated genes and 14 genes non-regulated by these hormones were studied using context computer analysis. consensus tgttct, previously found in dna fragments protected by glucocorticoid-receptor complexes from dnaase i digestion, was shown to be nonspecific for glucocorticoid-regulated genes. however, the analysis of sequences flanking the tgttct consensus has revealed that only glucocorticoid-regulated genes contain four regularl ...19863008884
glucocorticoid inhibition of c-myc, c-myb, and c-ki-ras expression in a mouse lymphoma cell line.glucocorticoid hormone treatment of certain t-cell-derived lymphomas and leukemias and of immature thymocytes results in cell death. furthermore, glucocorticoid-mediated killing of s49 mouse lymphoma cells appears to involve the control of the cell cycle; i.e., s49 cells treated with glucocorticoids are arrested in g1 of the cell cycle when events controlling cell proliferation occur. the protooncogenes, c-myc, c-myb, and c-ki-ras may be involved in cell cycle regulation and proliferation state ...19863008988
high murine mammary tumor virus expression in milk in a low mammary tumor mouse strain and high incidence of mammary tumor in hybrids produced by crossing with another low mammary tumor mouse strain.large amounts of murine mammary tumor virus (mmtv) were expressed in milk from a low mammary tumor mouse strain called ii-tes, established by crossbreeding dba/2 mouse strain with two strains of japanese pet mouse origin. the reciprocal hybrids of the ii-tes strain and oz-f strain, another low mammary tumor strain of japanese pet mouse origin, developed early-appearing mammary tumors at a high rate, and large quantities of mmtv were expressed in the milk. these findings suggest that different re ...19863009372
transfer, by selective breeding, of the pathogenic mtv-2 endogenous provirus from the gr strain to a wild mouse line free of endogenous and exogenous mouse mammary tumor virus.the gr laboratory mouse strain has five endogenous proviral copies of the mouse mammary tumor virus (mmtv). one of these, mtv-2, is unique because it causes mammary carcinomas in virtually 100% of breeding gr females prior to 1 year of age. to facilitate studies of this locus in particular, and mammary tumorigenesis in general, we genetically tailored a new mouse line, wxg-2, which bears mtv-2 as its only endogenous mmtv provirus. the wxg-2 line was constructed by making hybrids between the gr s ...19863009842
expression of the protein product of the mouse mammary tumor virus long terminal repeat gene in phorbol ester-treated mouse t-cell-leukemia cells.exposure of c57bl/6 mouse el-4 t-cell leukemia cells to phorbol ester (12-o-tetradecanoylphorbol-13-acetate) (tpa) induced the synthesis of protein products encoded by the mouse mammary tumor virus (mmtv) long terminal repeat (ltr) region. analysis of tpa-treated el-4 cells with antiserum raised against a synthetic peptide predicted by the mmtv ltr open reading frame sequence detected a polypeptide migrating in gels with an apparent molecular weight of 37,000 mr, as well as three less prominent ...19863009859
mammary tumorigenesis in feral mus cervicolor popaeus.a pedigreed breeding population of feral mus cervicolor popaeus with a high incidence of mammary tumors, arising between 6 and 14 months of age, is described. these mice were chronically infected with a type b retrovirus which is distantly related to the mouse mammary tumor virus (mmtv) of inbred strains of mus musculus. mmtv-induced mammary tumors in inbred mice frequently (80%) contained an insertion of the viral genome into the int-1 or int-2 loci of the tumor cellular genome. these two cellu ...19863009873
molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types a and b retrovirus genes.by using a dna fragment primarily encoding the reverse transcriptase (pol) region of the syrian hamster intracisternal a particle (iap; type a retrovirus) gene as a probe, human endogenous retrovirus genes, tentatively termed herv-k genes, were cloned from a fetal human liver gene library. typical herv-k genes were 9.1 or 9.4 kilobases in length, having long terminal repeats (ltrs) of ca. 970 base pairs. many structural features commonly observed on the retrovirus ltrs, such as the tataa box, po ...19863009897
[gene transplantation. studies of individual oncogenesis with transgenetic mice]. 19863009913
mechanism of gene regulation by steroid hormones.a first understanding of the molecular events on the dna level, underlying transcriptional regulation by steroid hormones, has been approached in the last 3 years by means of protein/dna interaction studies, using purified receptors. this work summarizes our knowledge of how purified glucocorticoid and progestine receptors interact with their cognate regulatory elements associated with polymerase ii dependent genes like mouse mammary tumour virus, the genes encoding human metallothionein iia, ch ...19863009974
functional analysis of the purified glucocorticoid receptor.glucocorticoid-receptor complex (gr) has been purified from rat liver by differential affinity for dna before and after activation, followed by ion-exchange chromatography. the purified gr has mol. wt 94,000 dalton. the protein contains three functional domains: (a) a steroid-binding domain; (b) a dna-binding domain; and (c) a domain necessary for normal biological function. a second protein, with mol. wt 72,000 dalton, copurifies with the gr. this protein does not bind steroid, does not interac ...19863009991
concerted activation of two potential proto-oncogenes in carcinomas induced by mouse mammary tumour virus.the induction of tumours by retroviruses lacking transduced oncogenes can involve the transcriptional or functional activation of cellular proto-oncogenes by an integrated provirus. thus, the two cellular genes int-1 and int-2, identified as common targets for activation by mouse mammary tumour virus (mmtv), may constitute previously unrecognized oncogenes. in tumours, proviral insertion at these loci leads to expression of messenger rnas which are undetectable in normal mammary glands. here we ...19863010125
control of cytochrome p1-450 gene expression: analysis of a dioxin-responsive enhancer system.we analyzed the function and sequence of a dioxin-responsive genomic element flanking the 5' end of the cytochrome p1-450 gene in high-activity variant mouse hepatoma cells. the element can regulate the mouse mammary tumor virus promoter. the element retains responsiveness to 2,3,7,8-tetrachlorodibenzo-p-dioxin (tcdd) when the distance, the 5' or 3' position, and/or the 5' or 3' orientation with respect to the promoter are varied. the function of the element requires tcdd-receptor complexes. the ...19863010318
consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development.we have constructed a transgenic mouse strain in which a mammary tumor virus ltr/c-myc fusion gene is anomalously expressed in a wide variety of tissues. the deregulated c-myc transgene, now glucocorticoid inducible, contributes to an increased incidence of a variety of tumors, including those of testicular, breast, lymphocytic (b cell and t cell), and mast cell origin. the deregulated gene does not, however, otherwise disturb cell proliferation, nor does it interfere with normal development in ...19863011271
physical state, expression and regulation of two glucocorticoid-controlled genes on bovine papilloma virus vectors.we have studied the extrachromosomal maintenance and the transcription regulation of two glucocorticoid-inducible genes on bovine papilloma virus (bpv) vectors in c127 mouse fibroblasts. these genetic elements were the rat tryptophan oxygenase (toase) gene promoter, which is active in vivo only in hepatocytes, and the long terminal repeat of the mouse mammary tumor virus (mmtv-ltr). from both genes, fusions of the 5'-flanking region of the transcription unit to the bacterial gene for chloramphen ...19863012094
direct detection of exogenous mouse mammary tumor virus sequences in lymphoid cells of balb/cfc3h female mice.the presence of exogenous mouse mammary tumor virus (mmtv) (c3h) dna sequences in lymphoid tissue (spleen, bone marrow, and thymus) and nonlymphoid tissue (liver and kidney) of balb/cfc3h female mice was directly assessed by dna hybridization methods. lymphoid tissues were found positive for integrated mmtv(c3h) sequences in females as young as 4 weeks. in most samples, the level of splenic mmtv(c3h) infection was low (2 to 5%). infection remained throughout the life of the animal. the percentag ...19863012113
sequence, topography and protein coding potential of mouse int-2: a putative oncogene activated by mouse mammary tumour virus.a major proportion of carcinomas induced by mouse mammary tumour virus (mmtv) show evidence for proviral activation of a cellular gene, int-2, on chromosome 7. the sequence of 7869 bp of dna spanning the transcription unit of int-2 was determined and compared with that of a series of int-2-specific cdna clones derived from mammary tumour rna. the predicted positions of intron-exon boundaries, established by alignment of cdna and chromosomal dna sequences, indicate that the gene comprises at leas ...19863013624
the endogenous mouse mammary tumour virus locus mtv-8 contains a defective envelope gene.the mtv-8 associated provirus, gr40, is not expressed in vivo. however, upon transfection into rat xc cells, the two mmtv specific mrnas of 35s and 24s are transcribed. further, the level of these transcripts is augmented when the transfected cells are grown in the presence of dexamethasone (ponta et al., 1983). no virus can be detected in the medium of the transfected cells. intracellular protein analysis of these transfected cells shows that although apparently authentic gag proteins are synth ...19863014784
16 alpha-hydroxylation of estradiol: a possible risk marker for breast cancer.from these results we may conclude that estradiol 16 alpha-hydroxylation is highly correlated with tumor incidence, and that the reaction is partly regulated by mmtv and the rest by genetic influences. elevated hydroxylation appears to be an autosomal dominant trait that is highly specific for estradiol. it is also pertinent that the product of the 16 alpha-hydroxyestrone reaction is a potent estrogen that is capable of binding covalently to amino acids and nucleotides, including the estrogen re ...19863014947
early pathologic changes in experimental and human breast cancer: facts and comments. 19863014948
regulatory sequences involved in the hormonal control of casein gene expression. 19863014951
destabilization of cytoplasmic mouse mammary tumor rna by heat shock: prevention by cycloheximide pretreatment.thermal stress of cultured mouse mammary carcinoma cells results in a rapid loss of basal and glucocorticoid-stimulated mouse mammary tumor virus (mmtv) rna. mmtv rna is almost nondetectable within 1-2 hr after a shift in the culture temperature to 42 degrees. actin mrna is stable over this time period. pretreatment of the cells with cycloheximide prevents the decay of mmtv rna. nuclear associated glucocorticoid receptor is not decreased but rather increased about 95% by the heat shock. the resu ...19863015134
mammary tumorigenesis in feral species of the genus mus. 19863015500
endogenous mmtv proviral genomes in feral mus musculus domesticus. 19863015501
differential expression of endogenous mouse mammary tumor virus genes during development of the balb/c mammary gland.expression of endogenous mouse mammary tumor virus sequences varied over the course of development of the mammary gland during primary pregnancy and lactation in virus-free balb/c mice. although rna from all regions of the genome was detected, both the level and temporal regulation of expression were different for long terminal repeat-, env-, and gag-pol-specific rnas. analysis of the methylation status of proviral dna indicated differential accessibility of the three endogenous units during dev ...19863016314
characterization, chromosome assignment, and segregation analysis of endogenous proviral units of mouse mammary tumor virus.in the course of analyzing sites of proviral integration in tumors induced by mouse mammary tumor virus (mmtv), we have isolated recombinant dna clones corresponding to the 5' and 3' ends of four endogenous mmtv proviruses present in balb/c and br6 mice. this has permitted the structural characterization of each locus by detailed restriction mapping and the preparation of dna probes specific for the cellular sequences flanking each provirus. these probes have been used to trace the segregation p ...19863016317
restriction endonuclease map of endogenous mouse mammary tumor virus loci in gr, dba, and nfs mice.mouse mammary tumor virus (mmtv) is integrated in the genome of most mice as an endogenous provirus. two of these mmtv proviral loci (mtv-1 and mtv-2) are associated with virus expression and tumorigenicity. we prepared restriction endonuclease maps of the endogenous mmtv proviruses in two strains, dba and gr, which contain the mtv-1 and mtv-2 loci, plus a third strain, nfs, which has a low mammary tumor incidence. we find that all these mouse strains have certain mmtv loci in common even though ...19863002033
a common mouse mammary tumor virus integration site in chemically induced precancerous mammary hyperplasias.mammary carcinomas can be induced by chemical and hormonal as well as viral carcinogens. irrespective of the class of inducer, these tumors develop in discrete stages, of which alveolar hyperplasia is one of the earliest identifiable. since carcinogenesis by the mammary tumor virus is now thought to involve proviral activation of adjacent cell genes at specific loci, we sought to determine if a similar mechanism also played a role in chemical and hormonal carcinogenesis and if its role was stage ...19863002039
the int-1 proto-oncogene.the int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. the gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. the functional sign ...19863332019
plasma levels of a viral protein during adjuvant treatment: reflection of murine mammary tumor status and therapeutic effect.the mouse mammary tumor and its associated virus, mouse mammary tumor virus, were chosen to test the possibility of using plasma levels of a mr 52,000 viral glycoprotein (gp52) as a means for monitoring changes in tumor status during surgical adjuvant cyclophosphamide:doxorubicin (adriamycin):5-fluorouracil treatment. analysis of tumor recurrence and plasma gp52 concentrations during the postoperative period demonstrated that both parameters were significantly decreased in the group receiving cy ...19863754489
immunocolloidal gold electron microscopy of viral antigens and cellular actin in c3h/he mouse mammary tumors.mouse mammary tumor virus (mmtv) antigens and cellular actin were visualized with protein a-coated colloidal gold at the ultrastructural level in c3h/he mouse mammary tumors using various antisera. observations with the postembedding method and statistical analyses of these data showed: (a) a glycoprotein with a molecular weight of 52,000 resided on the envelope of mature virions (b-particles), on the surface of budding particles, and on the vacuolar membrane, but not on intracytoplasmic a-parti ...19863756926
in vitro differentiation and progression of mouse mammary tumor cells.we have isolated clonal cell lines from a transplanted adenocarcinoma induced by the riii strain of mouse mammary tumor virus in a balb/c mouse. three major morphological cell types of these lines are developmentally linked; polygonal cells give rise to cuboidal and then to elongated cells. all cell lines expressed markers that are characteristic of mammary basal cells. in addition, the polygonal lines contained cells that have cell markers and ultrastructural features of epithelial cells; in th ...19863756929
nucleotide sequence analysis of the long terminal repeat of integrated caprine arthritis encephalitis virus.the nucleotide sequence of the long terminal repeat (ltr) of caprine arthritis encephalitis virus (caev), a prototype lentivirus was determined. 6-bp directly repeated host cell sequences flank the 376-bp proviral ltrs. by comparison with other retroviral sequences, the caev ltr likely contains u3, r and u5 regions 207, 86 and 83 base-pairs in length, respectively. sequences conforming to consensus transcriptional promoter sites were identified in the u3 region upstream of a potential transcript ...19863765821
mitogenic activity of the adenovirus type 12 e1a gene induced by hormones in rat cells.several lines of rat 3y1 cells in which expression of the adenovirus type 12 e1a gene can be regulated by dexamethasone were established by introduction of recombinant vector dna containing the adenovirus type 12 e1a gene placed downstream of the hormone-inducible promoter of mouse mammary tumor virus. these cell lines (gma cells) produced low basal levels of the e1a transcripts and proteins in normal medium and much higher levels upon addition of dexamethasone to the medium. when dexamethasone ...19862936902
glucocorticoid-regulated glycoprotein maturation in wild-type and mutant rat cell lines.glucocorticoid hormones can regulate the posttranslational maturation of mouse mammary tumor virus (mtv) precursor polyproteins in m1.54, a stably infected rat hepatoma cell line. we have used complement-mediated cytolysis to recover variants of m1.54 that fail to express mtv cell surface glycoproteins in a hormone-regulated manner (firestone, g.l., and k.r. yamamoto, 1983, mol. cell. biol., 3:149-160). one such clonal isolate, cr4, is similar to wild-type with respect to synthesis of mtv mrnas, ...19863023398
polypeptides of mason-pfizer monkey virus. iii. translational order of proteins on the gag and env gene specified precursor polypeptides.mason-pfizer monkey virus (m-pmv), the prototype d-type retrovirus, unlike most retroviruses, preassembles core structures in the cytoplasm of infected cells during morphogenesis. we have shown previously (j. bradac and e. hunter, 1984, virology 138, 260-275) that m-pmv virions contain 5 gag-encoded polypeptides. in this report, the translational order of the proteins encoded on the gag and env genes of m-pmv has been determined by pactamycin mapping. the proposed order of the viral proteins on ...19863485855
the 52 k protein: an estrogen regulated marker of cell proliferation in human mammary cells. 19863515355
inducible production of c-fos antisense rna inhibits 3t3 cell proliferation.antisense rna complementary to c-fos mrna was produced in mouse 3t3 cells by gene transfer techniques. transcriptional units were constructed consisting of a steroid-inducible mouse mammary tumor virus (mmtv) promoter, mouse or human 5' c-fos gene fragments in either the sense (5' to 3') or antisense (3' to 5') orientation, and splice and poly(a) signals from the human beta-globin gene. a gene that confers neomycin resistance was included in the vectors to allow isolation of stable transformants ...19863523478
molecular cloning and characterization of mouse mammary tumor proviruses from a t-cell lymphoma.five mouse mammary tumor virus proviruses and their flanking cellular dna sequences have been cloned from a transplanted c57bl/6 (b6) t-cell lymphoma containing additional copies of mouse mammary tumor virus dna. characterization of these proviruses and their flanking dna indicates that b6 lymphomas contain many newly integrated mouse mammary tumor virus copies synthesized by a mechanism(s) which generates polymorphism or deletions or both.19862867232
dependence of initiation of an innocent bystander cytotoxicity reaction on the association of viral antigens and tumor cell membranes in mice.in chemically induced mouse mammary tumors in balb/c mice, no murine mammary tumor virus (mumtv) antigens could be detected in the tumor cell membranes. in contrast, in mammary tumors of spontaneous appearance in balb/cfc3h mice neonatally infected with mumtv, viral antigens could be detected by immunofluorescence. specific activation of immune spleen lymphocytes in vitro by homologous tumor cell membrane preparations resulted in an innocent bystander cytotoxicity reaction in balb/c mice bearing ...19862871214
a preferred region for integration of friend murine leukemia virus in hematopoietic neoplasms is closely linked to the int-2 oncogene.gene mapping experiments show that fis-1, a preferred integration region for friend murine leukemia virus in hematopoietic neoplasms, is extremely closely linked to int-2, a preferred integration region for mouse mammary tumor virus in mammary carcinomas. studies at the rna and dna level prove that these loci are distinct.19862878090
ultrastructural characterization of the retrovirus particles (sm-mtv) liberated from the mammary tumor cell line (sm-mt) of a house musk shrew, suncus murinus (insectivora).detailed ultrastructure of a new type of retrovirus (sm-mtv) released by cultured cells (sm-mt) of a spontaneous mammary tumor from a house musk shrew suncus murinus, insectivora, is described. the virus particles were revealed as three forms: intracellular; budding; and extracellular. the intracellular type a particles were similar in profile to those associated with mouse mammary tumor cells and tended to form a small cluster of several particles in the cytoplasm. in addition, horseshoe-shaped ...19862421890
steroid regulation of transfected genes in mouse mammary tumour cells.the regulation of mouse mammary tumour virus (mmtv) rna by glucocorticoid hormones is well-established and has provided much information on how steroid hormones work. however, we have shown that androgens can also control mmtv rna accumulation in s115 mouse mammary tumour cells. this novel androgen action could be explained on the basis that the mmtv long terminal repeat (ltr) can respond to several classes of steroid if appropriate receptors are present in the cells. we have used transfection e ...19862422444
histological distribution of mtv antigen in mice detected by immuno-peroxidase staining.histological localization of mammary tumor virus (mtv) antigen was investigated using a variety of organs high (dd/tbr, shn, sln, gr) and low (balb/c) mammary cancer mice strains and immuno-peroxidase staining with mtv antigen. except for balb/c strain mice, the mammary gland and mammary tumors were generally positive. accessory male genital organs including the prostate, seminal vesicle, and coagulating gland also demonstrated a positive reaction, but the testis and female genital organs includ ...19862425548
reciprocal interference between milk-transmitted mammary tumor virus and friend leukemia viruses in mice: possible role of the interferon system.we have previously shown that mice simultaneously infected with the murine mammary tumor virus (mumtv) and with certain slow murine leukemia viruses (mlv) have an increased resistance to the pathological effects of both agents. here we report that milk-transmitted mumtv also delays the development of the acute erythroleukemia induced by friend leukemia virus (flv), and retards, or prevents in some cases, the development of long-term lymphomas caused by its helper component. this is confirmed by ...19862425940
circularization of retroviral genomic rna and the control of rna translation, packaging and reverse transcription.translation, packaging and reverse transcription of the genomic rna of retroviruses appear to be regulated by short and long range rna-rna interactions which take place within the 5'-600 nt and between the 5' and 3' untranslated sequences. the 5' (r and u5) and 3' (dr and u3) domains of the genomic rna together with the nucleic acid binding protein (nbp) would control the balance between the open state of the viral genomic rna, correlated with an efficient rna translation and the closed state, w ...19862427127
glucocorticoid agonists as well as antagonists are effective inducers of mouse mammary tumor virus rna in mouse mammary tumor cells treated with inhibitors of adp-ribosylation.glucocorticoids increase expression of specific genes by a mechanism involving binding to and "activation" of a specific receptor protein. other steroids, such as ru 486, bind to the glucocorticoid receptor but the resultant steroid-receptor complex is unable to activate glucocorticoid sensitive genes. in the present study we have observed that steroid regulation of the glucocorticoid-regulated mouse mammary tumor virus (mmtv) genome in cultured mouse mammary tumor cells is altered by treatment ...19862428821
two proto-oncogenes implicated in mammary carcinogenesis, int-1 and int-2, are independently regulated during mouse development.the int-1 and int-2 genes were first isolated as targets for transcriptional activation by proviral insertion mutations in mammary carcinomas induced by the mouse mammary tumor virus (mmtv). since these proto-oncogenes are not expressed at detectable levels in previously tested normal tissues from adult mice, we sought to determine whether these genes might be active during embryogenesis by examining mouse embryos and cultured teratocarcinoma cells for rna encoded by int-1 and int-2. a single si ...19862429320
murine mammary tumor virus pol-related sequences in human dna: characterization and sequence comparison with the complete murine mammary tumor virus pol gene.sequences in the human genome with homology to the murine mammary tumor virus (mmtv) pol gene were isolated from a human phage library. ten clones with extensive pol homology were shown to define five separate loci. these loci share common sequences immediately adjacent to the pol-like segments and, in addition, contain a related repeat element which bounds this region. this organization is suggestive of a proviral structure. we estimate that the human genome contains 30 to 40 copies of these po ...19862418214
mammary tumorigenesis and tumor morphology in four c3h sublines with or without exogenous mammary tumor virus.mammary tumorigenesis was surveyed in retired breeding females in four sublines of the c3h strain: in standard milk-transmitted early oncogenic mouse mammary tumor virus (mmtv)-infected c3h/he and c3h/ki mice, and in standard milk-transmitted early oncogenic mmtv free c3hf/he and c3hf/ki mice. all of 58 c3h/ki mice and 98% (306 of 309) of the c3h/he mice developed palpable mammary tumors at average ages of 276 and 284 days, respectively. thirty-one % (47 of 152) of the c3hf/ki mice and 77% (168 ...19862418961
effects of 5-azacytidine on expression of endogenous retrovirus-related sequences in c3h 10t1/2 cells.in a previous study (22) we found that transient exposure of c3h 10t1/2 mouse embryo fibroblasts to 5-azacytidine (5-azac) induced several changes in growth properties. the treated cells showed progressive changes in morphology, saturation density, growth rate, and serum dependence. by passage 5, the cells had acquired the ability to grow in 0.3% agarose, and by passage 30, they had given rise to fully transformed foci that grew in agarose, agar, and liquid suspension. this progression was rapid ...19862419582
sequence relationships of type d retroviruses which cause simian acquired immunodeficiency syndrome.simian acquired immunodeficiency syndrome (saids) in macaque monkeys is caused by type d retroviruses; three independent virus isolates are identified as srv-1 (saids retrovirus-serotype 1), srv-2, and mpmv (mason-pfizer monkey virus). virions from these three isolates have serologically related core antigens, but distinct surface proteins. also, srv-2 is unique since it apparently induces retroperitoneal fibromatosis in addition to saids. the complete dna sequence of molecularly cloned srv-2 is ...19872435057
silver enhancement of protein a-gold probes on resin-embedded ultrathin sections. an electron microscopic localization of mouse mammary tumor virus (mmtv) antigens.a simple method is described allowing the enhancement of the visibility of small gold probes for the electron microscopy. this method, which allows the silver intensification of gold directly on epon-embedded ultrathin sections, was used for the electron microscopic localization of mouse mammary tumor virus (mmtv) antigens in cultured cells derived from gr and balb/cfriii mouse mammary tumors. after the immunostaining with the preembedding protein a-gold technique, the ultrathin sections, placed ...19872437083
tenascin is a stromal marker for epithelial malignancy in the mammary gland.tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. the distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. an inhibition elisa, testing homogenates of rat tumors, confirm ...19872440026
ultrastructural and immunological studies of virus particles observed in a t-cell line derived from a mouse spontaneous lymphoma.intracytoplasmic type a virus particles in clusters, associated with budding, immature type b and mature type b-like particles were observed in a t-cell line derived from a spontaneous lymphoma of an a/j mouse. these particles shared the antigenic determinants with murine mammary tumor virus from riii, c3h, and gr strains as revealed by both indirect immunofluorescence and immunoperoxidase methods at ultrastructural level.19872440229
tumor-specific idiotype vaccines. iii. induction of t helper cells by anti-idiotype and tumor cells.in a previous report, we have demonstrated the induction of tumor-specific immunity by monoclonal anti-idiotype antibodies generated against a monoclonal anti-tumor antibody, 11c1, that also cross-reacts with mouse mammary tumor virus envelope glycoprotein gp52. also, we showed that whereas one anti-idiotype antibody, 2f10, could induce protective immunity, another anti-idiotype antibody, 3a4, induced nonprotective immunity. here we demonstrated the existence of t helper cells which recognize an ...19872442262
assessment of preferential cleavage of an actively transcribed retroviral hybrid gene in murine cells by deoxyribonuclease i, bleomycin, neocarzinostatin, or ionizing radiation.preferential cleavage induced by bleomycin, neocarzinostatin, or ionizing radiation in a transcribed cellular gene was evaluated through comparisons with deoxyribonuclease i. the glucocorticoid-inducible ltl gene (a hybrid viral gene derived from mouse mammary tumor virus dna) previously described [zaret, k. s., & yamamoto, k. r. (1984) cell (cambridge, mass.) 38, 29-38] served as the specific dna target. a southern blot analysis was used to specifically assess cleavage of the ltl gene in nuclei ...19872445373
glucocorticoid receptor binding to defined regions of alpha 2u-globulin genes.a dna-cellulose competition assay was used to study binding of glucocorticoid receptor complexes to two alpha 2u-globulin genes, rap 01 and rao 01. two binding regions were found in rap 01, one localized between bp -642 and -452, the other between -252 and -118 from the transcriptional initiation site. only the second region was found in rao 01. the binding affinity was comparable to that observed using a long terminal repeat fragment of mouse mammary tumor virus. both regions contain sequences ...19872447887
different adenovirus e1a-controlled properties of transformed cells require different levels of e1a expression.we have transformed primary baby rat kidney cells with a plasmid containing the adenovirus(ad)12e1 region in which the e1a promoter was replaced by the dexamethasone inducible mouse mammary tumor virus promoter. in the uninduced state the level of e1a expression is less than 10% of that in the induced state. we have investigated the effects of decreasing the levels of e1a on a number of e1a-mediated processes. first, expression of the e1b region is reduced several-fold upon reducing e1a expressi ...19872820846
isolation and characterization of minichromosome particles that contain a glucocorticoid-modulated promoter.a procedure for the enrichment of minichromosomes, composed of bovine papilloma virus and the long terminal repeat element of the mouse mammary tumor virus (mtv), from isolated nuclei is described. up to 60% of the minichromosomes were extracted as nucleoprotein particles. these particles sediment in sucrose gradients as 160s complexes. hormone-labeled glucocorticoid receptor co-purifies with these complexes in a specific fashion. between four and six molecules of receptor are bound per minichro ...19872821487
transcriptional repression of a hormone-responsive promoter.the activity of the mouse mammary tumor virus promoter was assessed in various sequence contexts with a transient transfection assay in which promoter activity was determined by way of expression of a linked gene encoding chloramphenicol acetyltransferase, as well as by direct analysis of rna transcripts. the results indicate that the proviral long terminal repeat contains a negative transcriptional control element in addition to the glucocorticoid-responsive transcriptional enhancer that has be ...19872821488
characterization of the dim series of balb/c preneoplasms for mouse mammary tumor virus-mediated oncogenesis.the dim series of preneoplasms, developed from the balb/c mammary cell line comma-d, and dim-derived tumors were examined for evidence of mouse mammary tumor virus (mmtv) involvement in the tumorigenic process. dim tissues were shown to be free of exogenous mmtv inasmuch as southern blot analysis of dnas extracted from dim preneoplasms and tumors showed the lack of a psti-generated 4.2-kilobase mmtv-gag-pol band. to examine the possibility of endogenous mmtv action via enhancer insertion, dnas f ...19872822232
sequence-specific positioning of nucleosomes over the steroid-inducible mmtv promoter.we have investigated chromatin organization over the mmtv ltr, a promoter regulated by steroid hormones. the studies were performed on cell lines containing bpv-based episomal constructs. nucleosome positioning was determined by localization of sites sensitive to the enzyme micrococcal nuclease, or to the chemical mpe-fe(ii). experiments with both reagents indicate that nucleosomes are specifically positioned in mmtv ltr chromatin. in the absence of hormone a regular cutting pattern is obtained, ...19872822386
molecular aspects of mouse mammary tumor virus biology. 19872822592
characterization of mouse mammary tumor virus gag-pro gene products and the ribosomal frameshift site by protein sequencing.the synthesis of retroviral polyproteins that are the translational products of the genome-size mrna is initiated in the upstream gag gene. the synthesis of the products of the protease gene (pro) and polymerase gene (pol) is regulated by translational suppression (in-frame read-through or frameshift) of termination codons as a strategy developed for controlling the level of replicative enzymes required only in catalytic amounts. in mouse mammary tumor virus (mmtv), three overlapping reading fra ...19872823251
[heterotopic production and tumorigenesis of mouse mammary tumor virus (mmtv)--can mmtv be a causative agent of lymphoid leukemias?]. 19872823474
current perspectives in the biology of mouse mammary tumour virus. 19872823501
induction of transcription by steroid hormones. 19872823900
progression to steroid insensitivity can occur irrespective of the presence of functional steroid receptors.a major problem in treatment of cancers arising in steroid-sensitive cells is their inevitable progression to a steroid-insensitive state; current therapies are based on the assumption that hormone insensitivity is associated with loss of receptor. we demonstrate for the first time that breast tumor cells can progress to steroid insensitivity in spite of functional steroid receptors. transfection of the steroid-inducible ltr-c3 gene into unresponsive s115 mouse mammary tumor cells results in ful ...19872824060
chromatographic purification and immunological analysis of viral polypeptides of mouse mammary tumor virus.the seven mouse mammary tumor virus (mmtv) structural polypeptides (gp52, gp36, p28, p23, p14, p12, and p10) were purified to apparent homogeneity. an improved and reproducible chromatographic method was used to obtain high yields of viral proteins from the same batch of isopycnically purified mmtv. the viral structural proteins were first extracted repeatedly with a high salt and high ph buffer in the presence of 1% triton x-100. loss of the minor viral proteins during column purification was m ...19872824547
analysis of the idiotypic network in tumor immunity.herein we have analyzed the expression of idiotopes associated with a monoclonal anti-tumor-associated antigen (taa) antibody in dba/2 mice which have progressively growing tumors or resist tumor growth. a panel of eight monoclonal antiidiotypic antibodies raised against a monoclonal antibody which reacts with a mouse mammary tumor virus cross-reactive qp52 envelope protein (taa) of the l1210/gzl lymphoma was used to measure the expression of idiotopes in sera from different treatment groups. si ...19872824616
[endogenous mmtv in the normal mammary gland and in dimethylanthracene-induced mammary cancer in balb/c mice].immunization of dmba-treated mice by the glycoprotein fraction from mammary glands of mice balb/c did not decrease the frequencies of induction of mammary tumors. this is in contrast to the results obtained during immunization by the formaldehyde treated preparation of mouse mammary tumor virus (mmtv). ecori and hindiii cleaved dna from the dmba-induced mammary tumors did not contain the additional virus specific fragments. in mammary tumors the expression of p27 mmtv was registered in contrast ...19872825005
a novel human nonviral retroposon derived from an endogenous retrovirus.in a human genome, we found dispersed repetitive sequences homologous to part of a human endogenous retrovirus termed herv-k which resembled mouse mammary tumor virus. for elucidation of their structure and organization, we cloned some of these sequences from a human gene library. the sequence common to the cloned dna was ca. 630 base-pairs (bp) in length with an a-rich tail at the 3' end and was found to be a sine (short interspersed repeated sequence) type nonviral retroposon. in this retropos ...19872825118
characterization of early molecular biological events associated with thymic lymphoma induction following infection with a thymotropic type-b retrovirus.a highly leukemogenic virus (dmba-lv) induces thymic lymphomas with a very short (40 days) latent period. all induced tumors contain low numbers of new integrated dmba-lv type-b proviruses and tumorigenicity of dmba-lv is completely abolished by a monoclonal antibody directed toward an envelope determinant present on a type-b mammary tumor-inducing viral isolate. while the dmba-lv type-b genome is very highly related to mammary tumor-inducing isolates it does have unique gp52 and p28 proteins as ...19872825409
morphological characterization of a granulocytosis/hypercalcemia-inducing murine mammary carcinoma cell line.a newly established cell line of a granulocytosis/hypercalcemia-inducing murine mammary carcinoma (ce mammary carcinoma) grown in serum-free culture medium secretes factors that stimulate proliferation of granulocytes and embryonal bone cells. these cultured cells retain the ability to produce granulocytosis and hypercalcemia when they are transplanted back into mice. in culture these cells form clusters of organized cells. studies by scanning, transmission, and freeze-fracture electron microsco ...19872825563
a subset of normal human b lymphocytes expresses an antigen cross-reactive with gp52 of murine mammary tumor virus.three monoclonal antibodies (mabs), ve7, vig3, and ixf9, that detect the 52-kd glycoprotein (gp52) of murine mammary tumor virus (mmtv) were tested for reactivity on normal human tonsillar lymphoid cells in an indirect immunofluorescence assay. two of the mabs, ve7 and vig3, reacted with subpopulations of b cells, whereas the third mab, ixf9, showed only very low-level reactivity with human lymphoid cells. ve7 and vig3 also reacted with small populations of peripheral blood lymphocytes, and all ...19872825999
prognostic factors in breast cancer--a pathological and immunological study of patients with stage 1 breast cancer.in order to analyze which features determine a poorer prognosis we undertook a study of 91 consecutive patients with pathological stage i breast cancer operated on at beth israel medical center (1968-71). tumor tissue slides were reviewed and features such as: tumor size, histologic type, nuclear grade, lymphocytic and perivenular lymphocytic infiltration, as well as sinus histiocytosis in the lymph nodes removed. records were reviewed and classified according to age and ethnic background. survi ...19872826257
interaction of different steroid hormones during progression of tumour cells to steroid autonomy.progression to steroid insensitivity poses a major problem in therapy of breast cancer, but studies of the origin of steroid-insensitive cells have been few and have concentrated in any one system on the loss of response to only one steroid. since both normal and tumour mammary cells have complex endocrine requirements, we wondered how different steroids might interact during loss of steroid sensitivity. cloned cells from the androgen-responsive shionogi 115 mouse mammary carcinoma respond in vi ...19872826338
identification of protein products encoded by the proto-oncogene int-1.the proto-oncogene int-1 is activated by adjacent insertions of proviral dna in mouse mammary tumor virus-induced tumors and has transforming activity in certain mammary epithelial cell lines. the gene is normally expressed in the central nervous system of mid-gestational embryos and in the adult testis. we raised antibodies against synthetic int-1 peptides and used these to identify protein products of the gene in cells transfected or infected with retroviral vectors expressing int-1. four prot ...19872828922
immunoelectron microscopic localization of mammary tumor virus (mtv) antigens in normal and cancerous mammary glands of mice.peroxidase-labeled fab' fragments of rabbit antisera against gp52 (major envelope protein) and a-particles of mammary tumor virus (mtv) were prepared and used for investigation by immunoelectron microscopy of the replication cycle of mtv-specific envelope and core antigens in normal and malignant mammary gland cells of female mice. the specificity of the antisera was proven by absorption tests and lack of reactivity to mtv-free mammary tissues. periodate-lysine-paraformaldehyde (plp) fixation su ...19872830473
glucocorticoid-resistant lymphoma cell variants that contain functional glucocorticoid receptors.a mouse t-lymphosarcoma cell line stably infected with mouse mammary tumor virus (mmtv) was used as the parent line for a genetic analysis of two glucocorticoid hormone responses, hormone-induced cytolysis and stimulation of viral gene expression. variants were selected for survival and elevated expression of mmtv proteins in the presence of the steroid. the mmtv marker provided a sensitive test for glucocorticoid receptor (gr) function in the hormone-resistant variants. this strategy resulted i ...19872830485
genetic evidence that the steroid-regulated trafficking of cell surface glycoproteins in rat hepatoma cells is mediated by glucocorticoid-inducible cellular components.the biological control of posttranslational maturation and compartmentalization reactions that operate upon proteins during transport to their final cellular destinations is crucial for normal cellular function. using the expression of mouse mammary tumor virus (mmtv) glycoproteins as sensitive probes in the viral-infected rat hepatoma cell line m1.54, we have discovered and documented a novel glucocorticoid-regulated trafficking pathway that controls the cell surface localization of mmtv glycop ...19872831239
identification of androgen response elements in mouse mammary tumour virus and the rat prostate c3 gene.the effect of steroid hormones on mouse mammary tumour virus (mmtv) promoter activity has been analysed in the breast cancer cell lines zr-75-1 and t-47d 11. both androgens and progestins were stimulatory in both cell lines, whereas glucocorticoids were stimulatory in only zr-75 cells. a glucocorticoid response was restored to t-47d cells by the transient expression of a glucocorticoid receptor expression vector, suggesting that endogenous receptors were limiting. the effect of androgen was medi ...19872831240
human monoclonal antibodies derived from pleural effusion lymphocytes of a patient with breast carcinoma react with human breast cancer-associated antigens and mouse mammary tumor virus polypeptides.four human hybridoma cell lines (peb1-4) were established from a fusion of pleural effusion lymphocytes isolated from a breast cancer patient with metastatic disease, 6 years postmastectomy. the hybridomas secreted igg-k (3 micrograms/ml/10(6) cells). these monoclonal antibodies (peb1-4) reacted to different degrees with mouse mammary tumor virus (mmtv) and t47d particles (humtv). immunological cross-reaction was also detected with antigens isolated from body fluids of breast cancer patients (bf ...19872832225
genetic mapping of prm-1, igl-1, smst, mtv-6, sod-1, and ets-2 and localization of the down syndrome region on mouse chromosome 16.molecular probes were used as markers in the backcross (czech ii x balb/cpt) x czech ii to determine the positions of six genes on mouse chromosome 16 (mmu 16). the order of the genes mapped is (centromere), protamine-1 (prm-1), immunoglobulin lambda 1 light chain (igl-1), preprosomatostatin (smst), an endogenous mouse mammary tumor virus locus (mtv-6), and two more distal sequences, superoxide dismutase, cytoplasmic form (sod-1), and the proto-oncogene sequence ets-2. the largest recombination ...19872882955
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