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a small region of the mouse mammary tumor virus long terminal repeat confers glucocorticoid hormone regulation on a linked heterologous gene.expression of mouse mammary tumor virus (mmtv) proviruses is transcriptionally regulated by glucocorticoid hormones. we have linked the mmtv long terminal repeat (ltr) to the coding region of the herpes simplex virus thymidine kinase gene and used this construction to characterize sequences within the ltr that are involved in glucocorticoid regulation. our results show that 290 base pairs (bp) of the mmtv ltr, including 190 bp upstream from the start site for transcription, are sufficient to con ...19836310597
breast cancer and mouse mammary tumor virus. 19836311069
sera from irradiated rats contain antibodies to a ubiquitous tumour-associated antigen.female rats of the inbred strains bn/birij and wag/rij were irradiated with 30 kv x-rays, or 15 mev or 0.5 mev fast neutrons. sera were collected several months after irradiation and found to be negative for antibodies reacting with the murine mammary tumour virus as tested by a solid-phase radioimmunoassay and an immunofluorescence absorption test. we found, however, that in an immunofluorescence assay several sera from irradiated rats reacted with a cytoplasmic antigen in rat mammary, ureter a ...19836311562
evidence for a prokaryotic promoter in the murine mammary tumor virus long terminal repeat.the long terminal repeat (ltr) of c3h murine mammary tumor virus (mumtv) is approx. 1.3 kb long. haeiii digestion of a cloned psti fragment containing the left-end ltr generated four fragments of sizes 0.56, 0.41, 0.34 and 0.14 kb, one of which (0.41 kb) had a promoter activity in escherichia coli. this was demonstrated by replacing the bacterial promoter for the neomycin-resistance (nmr) gene in the plasmid pkc56 with the haeiii fragments. only the 0.41-kb fragment that contains sequences from ...19836311680
molecular biological characterization of a highly leukaemogenic virus isolated from the mouse. iii. identity with mouse mammary tumour virus.a highly leukaemogenic virus isolate (dmba-lv) endogenous to the cfw/d mouse has been found to contain two viral genomes. one was closely related to the type b milk-borne mouse mammary tumour virus (mmtv) and present in tenfold excess over a type c viral genome which was only partially related to xenotropic and polytropic isolates from the cfw/d mouse as well as to the ecotropic moloney murine leukaemia virus isolate. the thymic lymphoma cell line that produced dmba-lv expressed high levels of m ...19836311950
sheep pulmonary adenomatosis: demonstration of a protein which cross-reacts with the major core proteins of mason-pfizer monkey virus and mouse mammary tumour virus.a retrovirus that causes pulmonary adenomatosis, a contagious lung tumour of sheep, contains a 25 000 mol. wt. polypeptide which cross-reacts with the major core protein (p27) of mason-pfizer monkey virus and mouse mammary tumour virus.19836311958
nucleotide sequencing of an apparent proviral copy of env mrna defines determinants of expression of the mouse mammary tumor virus env gene.to extend our understanding of the organization and expression of the mouse mammary tumor virus genome, we determined the nucleotide sequence of large regions of a cloned mouse mammary tumor virus strain c3h provirus that appears to be a dna copy of env mrna. in conjunction with analysis of several additional clones of integrated and unintegrated mouse mammary tumor virus dnas, we came to the following conclusions: (i) the mrna for env is generated by splicing mechanisms that recognize conventio ...19836312081
amplification and hormone-regulated expression of a mouse mammary tumor virus-eco gpt fusion plasmid in mouse 3t6 cells.mouse 3t6 cells were transformed with a chimeric dna plasmid, psvmgpt, in which the mouse mammary tumor virus (mmtv) promoter was fused to the escherichia coli gene encoding xanthine-guanine phosphoribosyl transferase (eco gpt). the transformants exhibited glucocorticoid-inducible expression of eco gpt. with limiting xanthine concentrations, conditions were established in which cell growth became hormone dependent. cells selected for their ability to grow in limiting concentrations of both xanth ...19836312292
widespread occurrence in mammals of antibodies reactive to intracytoplasmic a particles of the mouse mammary tumor virus.serum antibodies reactive to clusters of intracytoplasmic a particles in mouse mammary tumors and leukemia cells by means of an indirect immunofluorescence assay were detected in 11 mammalian species (ranging in frequency from 5.1 to 29.3%). these antibodies could not be found in sera from chicken, ducks and geese. their presence in so many mammalian species, not only in mammary tumor virus-infected mice, sheds new light on similar antibodies in man detected 10 years ago.19836312921
nucleotide sequence of the 5' noncoding region and part of the gag gene of mouse mammary tumor virus; identification of the 5' splicing site for subgenomic mrnas.we have determined the sequence of the first 1371 nucleotides at the 5' end of the genome of mouse mammary tumor virus using molecularly cloned proviral dna of the gr virus strain. the most likely initiation codon used for the gag gene of mouse mammary tumor virus is the first one, located 312 nucleotides from the 5' end of the viral rna. the 5' splicing site for the subgenomic mrna's is located approximately 288 nucleotides downstream from the 5' end of the viral rna. from the dna sequence the ...19836314267
glucocorticoid regulation of gene expression: mouse mammary tumor virus as a model system. 19836314448
lobuloalveolar differentiation and tumorigenesis: two separate activities of mouse mammary tumor virus.the morphological growth of the mammary glandular tree from 3 to 18 months of age has been quantified in three groups of genetically identical virgin female mice: balb/c mice free of milk-transmitted mouse mammary tumor virus (mmtv) infection and balb/cfc3h and balb/cfriii mice carrying milk-transmitted mmtv infection of c3h or riii origin, respectively. mice were killed at 3-month intervals, and their mammary glands were prepared for stereoscopic examination as whole mounts. any cluster of alve ...19836315219
molecular genetics of mouse mammary tumor virus. 19836315306
mouse mammary tumor virus expression and mammary tumor development. 19836315307
regulation of mouse mammary tumor virus gene expression by glucocorticoid hormones. 19836315308
unusual findings of viral production (mumtv) in murine mammary tumors (balb/cfc3h).some unusual findings of the murine mammary tumor virus (mumtv) are described in cells of balb/cfc3h mice mammary tumors: (1) a conspicuous endocellular production of b particles by budding of a particles into small and large cytoplasmic vacuoles, into intracytoplasmic lumina, and possibly into vacuoles of secretion; (2) an extracellular production of b particles (in addition to the classic budding via microvilli) by opening at the cell surface of intracytoplasmic lumina containing mature and im ...19836315481
the proviral dna of mouse mammary tumor virus: its use in the study of the molecular details of steroid hormone action. 19836315504
alterations of acquired mouse mammary tumor virus dna during mammary tumorigenesis in balb/cfc3h mice.the patterns of the milk-transmitted (exogenous) mouse mammary tumor virus (mumtv) dna restriction endonuclease fragments in the nodule and tumor stages of balb/cfc3h mouse mammary neoplasia were compared with the use of the southern blot analysis. acquired mumtv restriction fragments were detected in dna from hyperplastic alveolar nodules (han), from primary hyperplastic outgrowths (hpo), from families of transplanted hpo, from tumors from hpo, and from serially transplanted tumors. the restric ...19836316008
sequence-specific binding of glucocorticoid receptor to mtv dna at sites within and upstream of the transcribed region.glucocorticoid receptor protein stimulates transcription initiation within murine mammary tumor virus (mtv) dna sequences in vivo, and interacts selectively with mtv dna in vitro. we mapped and compared five regions of mtv dna that are bound specifically by purified receptor; one resides upstream of the transcription start site, and the others are distributed within transcribed sequences between 4 and 8 kb from the initiation site. each region contains at least two strong binding sites for recep ...19836317184
anti-glucocorticoids block the enhancement of mouse mammary tumor virus production by 12-o-tetradecanoylphorbol-13-acetate.four anti-glucocorticoids, 11-deoxycortisol, deoxycorticosterone, 17 alpha-methyltestosterone and progesterone were demonstrated to antagonize the stimulation of mouse mammary tumor virus (mmtv) production by the glucocorticoid hormone dexamethasone in the cell line mm5mt. these same anti-glucocorticoids were also able to suppress the enhancement of mmtv production by the tumor promoting phorbol ester, 12-o-tetradecanoylphorbol-13-acetate (tpa), whereas estradiol, the anti-tumor promoter trans-r ...19836317217
adp-ribosylation of chromosomal proteins and mouse mammary tumor virus gene expression. glucocorticoids rapidly decrease endogenous adp-ribosylation of nonhistone high mobility group 14 and 17 proteins.the relationship between endogenous adp-ribosylation of chromosomal proteins and glucocorticoid-regulated mouse mammary tumor virus gene expression was investigated in cultured mouse mammary tumor cells. it was observed that glucocorticoids quickly decreased endogenous (adp-ribose)n on the nonhistone high mobility group (hmg) 14 and 17 proteins. the half-time for this loss was 8 and 17 min, respectively, for the two proteins. (adp-ribose)n on hmg 1 and 2 and on histone h1 was less susceptible to ...19836317693
mouse mammary tumor virus: specific methylation patterns of proviral dna in normal mouse tissues.the methylation state of endogenous mouse mammary tumor virus (mumtv) proviral dna was examined in normal mouse tissues. dnas from various tissues were cleaved with the methylation-sensitive enzymes hhai and hpaii and analyzed by southern blotting. tissue-specific mumtv proviral dna methylation patterns were found in the balb/c, c3h, c57bl, gr/a, and gr-mtv-2- mouse strains. mumtv proviral dna was hypomethylated in dnas from the spleens and testes of all strains examined. the gr/a mouse strain, ...19846317895
amplification and novel locations of endogenous mouse mammary tumor virus genomes in mouse t-cell lymphomas.endogenous mouse mammary tumor virus genomes are amplified and located in novel cell dna sequences in many mouse t-cell lymphomas. transplanted tumors recovered from the same mouse strain and shown to be of independent origin by chromosomal analysis, by the presence of jh immunoglobulin gene rearrangements, or by the integration patterns of exogenous moloney mulv genomes frequently showed similar patterns of novel mouse mammary tumor virus-containing cell dna fragments. this process of amplifica ...19846317898
proliferative responses of mouse mammary glands to 17 beta-estradiol and progesterone and modification by mouse mammary tumor virus.the responses of mammary glands of ovariectomized mice to 17 beta-estradiol and progesterone were measured by mitotic and [3h]thymidine-labeled indices in low-tumor c57bl mice and high-tumor br6 mice. the br6 mice were subdivided into those carrying murine mammary tumor virus (mumtv) and those that had been freed from it by foster nursing. in all groups, continuous stimulation by the two hormones administered together resulted in a cell proliferation peak. the magnitude of response varied accord ...19836317935
glucocorticoid regulation of transcription at an amplified, episomal promoter.the mouse mammary tumor virus long terminal repeat (mmtv ltr) has been introduced into cultured murine cells, using the 69% transforming fragment of bovine papilloma virus type 1 (bpv). transformed cells contain up to 200 copies of the chimeric molecules per diploid genome. the restriction endonuclease map of the acquired recombinants, as well as the physical structure of the dna, indicates that the ltr-bpv molecules present in these cells occur exclusively as unintegrated, extrachromosomal epis ...19836318079
mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15.most mammary carcinomas induced in c3h mice by the mouse mammary tumour virus (mmtv) bear a new proviral insertion within a highly conserved locus on chromosome 15 called int-1. a transcriptional unit within this locus is inactive in all tested normal tissues but expressed at low levels in mammary tumours with proviral insertions positioned on either the 5' and 3' sides of the gene. transcription of the proviruses proceeds away from int-1; thus an indirect mechanism appears to activate expressio ...19846318122
correlation of glucocorticoid receptor binding sites on mmtv proviral dna with hormone inducible transcription.steroid hormones, when complexed to their receptors, recognize and bind specific dna sequences and subsequently induce increased levels of transcription. the mechanisms of steroid hormone action were analyzed by constructing chimeric dna molecules from portions of mouse mammary tumor virus envelope and long terminal repeat (ltr) regions ligated to the thymidine kinase (tk) gene of herpes simplex virus. this construction allowed the tk gene to be expressed in a hormone-responsive fashion upon tra ...19836318311
effect of malignant transformation upon the cellular retinoid binding proteins in cultured murine mammary cells.cellular retinol (crbp) and retinoic acid binding proteins (crabp) were measured in normal (c57bl) and murine mammary tumor virus (mumtv)-induced murine mammary tumor cells (c57blfriii) grown in monolayer culture. high speed supernatant fractions (cytosols) from transformed cells contained elevated levels of crbp and crabp (0.276 and 1.410 pmol/mg protein, respectively) compared to cytosol from non-transformed murine mammary cells which contained only low levels of crbp (0.099 pmol/mg protein). ...19836318967
peroral infection of suckling mice with milk-borne mouse mammary tumour virus: uptake of the main viral antigens by the gut.persistence of mouse mammary tumour virus (mmtv) components in the digestive tract of suckling mice was investigated by immunoperoxidase staining of the main viral antigens and micro-immunoenzyme assays of gp52 and p28; these latter assays were also performed after ingestion of milk enriched in viral antigens using cr2o3 as a marker for the alimentary bolus migration. when compared to the ingested antigens, the amounts of gp52 and p28 decreased during transit, p28 being more rapidly digested tha ...19836319548
expression of a viral oncogene under control of the mouse mammary tumor virus promoter: a new system for the study of glucocorticoid regulation. 19836320286
increased level of immunoreactive enkephalins in the brain of tumor-bearing mouse.balb/c mice with emt6-ky mouse mammary tumor were assayed for the immunoreactive content of enkephalins in the brain by radioimmunoassay. brains of tumor-bearing mice had approximately 22 percent more immunoreactive enkephalins than those of the controls.19836320320
characterization and chromosomal location of endogenous mouse mammary tumor virus loci in gr, nfs, and dba mice.endogenous mouse mammary tumor virus (mmtv) proviral copies were characterized in three genetically dissimilar mouse strains: gr, a high-tumor-incidence strain bred in europe that carries an mmtv proviral copy associated with early mammary tumors; dba, a high-tumor-incidence laboratory strain bred in the usa with an endogenous copy that is associated with mmtv antigen expression in the milk; and nfs, a recently inbred line of the low-tumor-incidence nih swiss mouse. mmtv proviral loci were studi ...19846320529
cystic hypersecretory duct carcinoma of the breast.this report describes a grossly and microscopically distinctive multicystic form of duct carcinoma of the breast which we have termed cystic hypersecretory duct carcinoma. the outstanding morphologic feature is marked secretory activity with the formation of dilated ducts and cysts containing homogeneous, eosinophilic material which resembles thyroid colloid. the inconspicuous epithelium lining the cysts gives rise to micropapillary carcinoma which also occurs in associated ducts. a biopsy that ...19846320685
sequences related to mouse mammary tumor virus genome in tumor cells and lymphocytes from patients with breast cancer.cloned murine mammary tumor virus (mumtv) sequences allowed us to search for murine mammary tumor virus related sequences in the dna of surgically removed human breast tumors. out of 28 tumors so far examined two were found to contain an eco ri dna fragment homologous to the long terminal repeat-group antigen (ltr-gag) and the envelope (env) sequences of mumtv. we have taken the lymphocytes of these patients and cultured them. rapid growth of lymphocytes, mostly of t origin, occurred in the pres ...19846320830
dna sequences involved in the regulation of gene expression by glucocorticoid hormones. 19846320889
increased incidence of mouse mammary tumor virus-related antigen in tunisian patients with breast cancer.biopsies obtained from 74 tunisian women with breast cancer (33 cases), benign breast disease (17 cases), and cervical cancer (24 cases) were assayed for the presence of an antigen cross-reacting with gp52 of the mouse mammary tumor virus (mmtv) in order to determine the frequency and possible prognostic significance of this antigen in a form of rapidly progressing breast cancer designated poussée évolutive or pev. antigen was detected in 23/33 breast carcinomas (70%) but in none of the 41 contr ...19846321360
two genetically transmitted balb/c mouse mammary tumor virus genomes located on chromosomes 12 and 16.we have examined ecori-restricted cellular dna from balb/c mouse-hamster somatic cell hybrids by blot hybridization for the presence of mouse mammary tumor virus-related sequences. results of this analysis show that mouse mammary tumor virus-related proviral copies are located on chromosomes 16 (16-kilobase-pair fragment) and 12 (10.5- and 7.7-kilobase-pair fragments).19846321750
increased concentration of an indigenous proviral mouse mammary tumor virus long terminal repeat-containing transcript is associated with neoplastic transformation of mammary epithelium in c3h/sm mice.increased amounts of mouse mammary tumor virus (mmtv) proviral transcripts were found in rna dot blots from mmtv-negative, c3h/sm mouse mammary tumors which arose spontaneously or were induced by hormonal or chemical carcinogens or both. other dot blots probed with a long terminal repeat (ltr) probe showed that ltr (mmtv)-containing transcripts were disproportionately represented in these tumor rnas. different segments of the mmtv genome were used in sequential hybridizations to northern blots t ...19846321767
asymmetric transcription of mouse mammary tumor virus genes in vivo and in vitro.mouse mammary tumor virus (mmtv) dna fragments were cloned into m13 bacteriophage, and the single-stranded recombinant phage dnas were used as strand-specific nucleic acid hybridization probes to measure synthesis of plus (genomic) and minus strands of mmtv rna in cultured cell lines and in cell-free preparations of nuclei. pulse-labeling studies showed that synthesis of mmtv rna in three different cell lines was highly asymmetric. in nuclear preparations from a cloned line of mmtv-infected rat ...19846321800
indirect leukocyte migration inhibition in breast cancer and benign breast disease patients by mouse mammary tumor virus grown in feline kidney cells.indirect migration inhibition assays were performed with normal and mammary tumor-bearing c3h/hen mice and patients with breast disease to assess cellular immunity against three different mouse mammary tumor virus (mtv) preparations grown in feline kidney cell cultures and against a mouse-derived mtv preparation. mtv obtained after passage through feline kidney cells and the mouse-derived mtv were capable of eliciting macrophage migration inhibitory factor production by mouse spleen cells obtain ...19846321840
mouse mammary tumor virus integration regions int-1 and int-2 map on different mouse chromosomes.two regions of mouse dna which constitute common provirus integration sites in tumors induced by mouse mammary tumor virus have been identified and designated int-1 and int-2. by examining a series of hamster-mouse somatic cell hybrids, we mapped the int-2 locus to mouse chromosome 7 and confirmed the previous assignment of int-1 to chromosome 15. this constitutes proof that int-1 and int-2 are discrete genetic loci. it is therefore possible that proviral activation of two distinct cellular gene ...19846321961
hormone-dependent enhancement of neoplastic phenotype expression by mumtv-infected heterologous cells, and mumtv-induced cellular antigens.a new property, i.e. acquisition of insulin (insulin + dexamethasone)-mediated enhancement of anchorage independence by heterologous mumtv-infected cells, is described. hormone-mediated anchorage-independent growth enhancement in mumtv-infected cells is followed by expression of a cell-surface antigen, recognized by allogeneic (c3h----akr) anti-thy 1.2 antigen serum. the absorption test and the use of monoclonal antibody to the thy 1.2 antigen showed that hormone-dependent antigen on the cell su ...19846323329
dexamethasone-stimulated expression of a proviral copy of mouse mammary tumor virus env mrna.the kinetics of dexamethasone induction of mouse mammary tumor virus rnas in a cell line (designated line 8) which contains a deleted proviral dna has been examined. this dna is an apparent reverse transcription product of the env mrna. a detectable increase in the 3.8-kilobase rna (mouse mammary tumor virus env mrna) was present within 15 min after hormone addition. the 2.5-kilobase rna detected previously during hormone induction studies was also observed in these cells. both rnas increased in ...19846323764
structure and specific dna binding of the rat liver glucocorticoid receptor.during recent years major advances have been made in our understanding of glucocorticoid mechanism of action. this progress has been made possible by access to purified glucocorticoid receptor in significant amounts as well as by application of hybrid dna technology within the field of glucocorticoid control of gene expression. especially the mammary tumour virus genome has turned out to be a convenient experimental system suitable for such investigations. this paper summarizes some of the work ...19846323858
[introduction of foreign genes into eukaryotic cells using retrovirus as a vector]. 19836324284
[studies on cellular differentiation by gene transfer]. 19836324287
multiple genetic factors in the mhc and predominant role of d-end in the resistance against c3h-mtv-induced mammary tumors. 19836324428
mouse mammary tumor virus can mediate cell fusion at reduced ph.mouse mammary tumor virus, a type-b retrovirus, was shown to mediate fusion of cultured cells following low-ph treatment. fusion could be demonstrated both with virus-infected cells or with uninfected cells carrying freshly absorbed virus. although the fusion response was variable between different cell lines, one line of mmtv-infected mink lung cells, designated mgr4, was particularly susceptible to fusion at reduced ph. since expression of mmtv in these cells is strongly regulated by glucocort ...19846324459
the glucocorticoid receptor in rat liver. 19846324803
expression of mammary tumor virus proteins in preneoplastic outgrowth lines and mammary tumors of balb/cv mice.a subline of balb/c mice, designated balb/cv, has been segregated which exhibits an intermediate mammary tumor incidence and which harbors a unique milk-transmitted virus. six stable hyperplastic alveolar nodule outgrowth lines were established from chemical carcinogen-treated and hormonally stimulated mice. tumor incidences exhibited by the individual preneoplastic lines ranged from 22 to 95%; no differences in tumor-producing capability were observed when lines were transplanted in virus-negat ...19846324998
the region of mouse mammary tumor virus dna containing the long terminal repeat includes a long coding sequence and signals for hormonally regulated transcription.starting from a biologically active recombinant dna clone of exogenous unintegrated gr mouse mammary tumor virus, we have generated three subclones of psti fragments of 1.45, 1.1, and 2.0 kb in the plasmid vector pbr322. the nucleotide sequence has been determined for the clone of 1.45 kb which includes almost the complete region of the long terminal repeat (ltr) plus an adjacent stretch of unique sequence dna. a short region of the 2.0 kb clone, containing the beginning of the ltr, has also bee ...19826325151
comparison of mammary tumor development in mice bearing pituitary implants & carrying mammary tumor virus infections by various routes. 19836325333
activation of cellular gene by mouse mammary tumour virus may occur early in mammary tumour development.there is now good evidence that the induction of mammary carcinomas by mouse mammary tumour virus (mmtv) involves provirus activation of specific cellular genes. thus, a high percentage of virally induced tumours contain an acquired mmtv provirus in either of two defined integration regions, termed int-1 and int-2, and provirus insertion is accompanied by expression of specific rna transcripts from these regions. we show here that in some recurring, pregnancy-dependent mammary tumours provirus i ...19846325949
[humoral antibodies to the antigens related to the structural protein antigens of the mammary cancer virus (mtv) in breast cancer patients and in healthy donors].indirect radioimmunoassay and immunoperoxidase studies provided further evidence of human serum reactivity with murine mammary tumor virus (mmtv) structural proteins. examination of over 400 human sera from breast cancer (bc) patients and controls has shown that the incidence of antibodies which react with mmtv structural proteins was significantly higher in bc patients (50%) than in patients with carcinomas of other organs (3%) or normal women (3%). however, the percentage of subjects immune to ...19846326892
tumorigenesis by mouse mammary tumor virus: proviral activation of a cellular gene in the common integration region int-2.approximately 50% of tumors induced by mouse mammary tumor virus (mmtv) contain an acquired provirus within a limited region of chromosomal dna, termed int-2. we have extended our previous characterization of this locus and have mapped provirus integration sites in 21 independent tumors. although integration occurs at multiple sites, proviruses within int-2 are distributed into two oppositely oriented groups whose transcription is directed away from a central domain. provirus insertion in int-2 ...19846327073
glucocorticoid receptors recognize dna sequences in and around murine mammary tumour virus dna.in several rodent cell lines, glucocorticoids increase the transcription of murine mammary tumour virus (mmtv) proviral dna in a process mediated by the glucocorticoid receptor. to investigate whether a direct interaction between the receptor and specific sequences on the induced genes can be implicated in the hormonal regulation of transcription, filter binding studies were performed with partially purified glucocorticoid receptor of rat liver and eight cloned mmtv proviral probes. both the 40 ...19826327283
dna binding properties of glucocorticosteroid receptors bound to the steroid antagonist ru-486.ru-486 is an anti-fertility steroid which also has anti-glucocorticosteroid effects. ru-486 is shown to be a strong antagonist of the glucocorticosteroid-induced cytolytic response of the murine thymoma lines w7tb and t1m1b , and of the induction of mouse mammary tumor virus (mmtv) mrna in t1m1b cells. the glucocorticosteroid receptor of w7 cells has high affinity for ru-486 (kd = 3 x 10(-9) m) but the complex formed has low nuclear transfer capacity. binding of ru-486, as compared with the gluc ...19846327286
expression of xenotropic-like env rna sequences in normal dba/2 and nzb mouse tissues.using a dna probe prepared from cloned env gene sequences of friend spleen focus-forming viruses, we detected the differential expression of multiple rna species in uninfected dba/2 fibroblasts and in various tissues from adult dba/2 and nzb mice. the size of the major rna species detected was estimated to be 24s . the 24s rna species was enriched in polyadenylate-selected preparations and thus may represent a message for endogenous viral envelope glycoproteins. the viral origin of the 24s rna w ...19846328045
functional analysis of the steroid hormone control region of mouse mammary tumor virus.gene fusions between the mouse mammary tumor virus long terminal repeat and the e. coli lacz gene have been shown to exhibit hormone dependent expression of beta-galactosidase activity. these constructions were used in transient expression experiments to assess the effects of specific modifications introduced into the region upstream of the transcription initiation site. 5' deletions demonstrate that sequences sufficient for wild-type promoter function are contained downstream of residue -64 rel ...19846328415
contacts between hormone receptor and dna double helix within a glucocorticoid regulatory element of mouse mammary tumor virus.glucocorticoid hormones enhance the transcription of mouse mammary tumor virus dna by mechanisms involving a direct interaction of the hormone receptor with four binding sites in a glucocorticoid regulatory element located between -72 and -192 base pairs upstream of the main transcription initiation site within the proviral long terminal repeat regions. methylation at the n-7 position of any of three g residues within one of the binding sites prevents binding of the receptor. in addition, in the ...19846328488
factors that affect metastasis in virus-induced mouse mammary tumors.two hundred and forty-one mammary tumor-bearing breeding female mice of the balb/cf c3h and balb/ cfriii strains, carrying milk-transmitted murine mammary tumor virus (mumtv) of c3h and riii origin, respectively, were studied to evaluate the factors that affect tumor metastasis. only lung metastases were considered and the following factors taken in account: mumtv inducing variant (c3h, riii), number of deliveries, tumor histotype , number of tumors per mouse, clinical duration of tumors, tumor ...19846328713
mouse mammary tumor virus: transcriptional control and involvement in tumorigenesis. 19846328901
the chromosomal integration site determines the tissue-specific methylation of mouse mammary tumour virus proviral genes.multiple endogenous mouse mammary tumour virus (mmtv) proviral genes are present at different chromosomal locations in inbred mouse strains. proviral dna methylation is location and tissue specific. the methylation patterns are stably inherited and appear to be conferred upon the viral dna by the flanking mouse genomic dna. in transformed cells, either mammary carcinoma cells, or cells immortalized by sv40 in vitro, the stable pattern of methylation is lost. although hypomethylation of proviral ...19846329738
purification and partial characterization of a murine mammary tumor-associated antigen.a mammary tumor-associated antigen (mtaa) of the murine mammary tumor virus (mumtv)-induced spontaneous mammary tumors of c3h/j mice was purified and partially characterized. the crude extract of the mammary tumor, when subjected to deae-cellulose chromatography and eluted with a discontinuous nacl gradient, provided three major protein peaks, of which only the first (f1) possessed the mtaa activity. the antigen was further purified by subjecting f1 to polyacrylamide gel electrophoresis. the mta ...19846329884
immunological relatedness of a murine mammary tumor-associated antigen and human breast cancer.immunological relatedness of a non-virion, murine mammary tumor-associated antigen (mtaa) and human breast cancer was demonstrated in this study. the mtaa was isolated from spontaneous mammary tumors (mmt) of c3h/j mice. an anti-serum specific for the mtaa was prepared by exhaustively absorbing the rabbit anti-serum to the mmt extract with tissue pellets of the pooled organs of tumor-free female mice. the observed cross-reaction of human malignant breast tumor (mbt) tissues with the absorbed ant ...19846329885
the human genome contains multiple sequences of varying homology to mouse mammary tumour virus dna.sequences related to the mouse mammary tumour virus (mumtv) dna were isolated from a genomic library of human dna by screening under conditions of relaxed stringency. it is estimated that there are in the order of 50 mumtv-like sequences per haploid genome and that the homology between the different human sequences and mumtv varies by 15%.19846329918
early events in the stimulation of mammary tumor virus rna synthesis by glucocorticoids. novel assays of transcription rates.two procedures were devised to examine initial events in the glucocorticoid-regulated transcription of integrated murine mammary tumor virus (mtv) dna sequences. first, cells in monolayer culture were exposed for brief periods to dexamethasone and then permeabilized in situ with digitonin to allow entry of 32p-labeled ribonucleoside triphosphates and measurement of transcription rates. the results revealed that the rate of mtv rna synthesis is stimulated selectively by dexamethasone after an app ...19846330056
[glucocorticoid receptors and gene regulation]. 19846330477
dexamethasone increases the number of rna polymerase ii molecules transcribing integrated mouse mammary tumor virus dna and flanking mouse sequences.in mouse ltk- cells that were transfected with recombinant bacteriophage dna containing a complete proviral copy of an integrated endogenous mouse mammary tumor virus (mmtv) with its flanking cellular sequences, the newly acquired mmtv proviruses were transcribed in a glucocorticoid-responsive fashion. after hormone treatment of selected cell clones in culture we isolated the nuclei, elongated the nascent rna chains in vitro, and determined the number of rna polymerase ii molecules on the transc ...19846330527
properties of retrovirus-like particles produced by a human breast carcinoma cell line: immunological relationship with mouse mammary tumor virus proteins.clonal derivatives 8 and 11 of the t47d human breast carcinoma cell line release particles that have the biochemical characteristics of a retrovirus. particles recovered from cultures of [3h]uridine-labeled clone 11 had a density of 1.18 g/ml and contained 60-70s and 35s rnas associated with reverse transcriptase activity. the production of these particles was steroid-dependent. clone 8 particles had a higher density, 1.195 g/ml, and their production was independent of steroid hormone. by ria, a ...19846330748
fine structure analysis and surface characteristics of mouse mammary gland adenocarcinomas.mammary adenocarcinomas from c3h/hej mice carrying the mammary tumor virus were studied by means of light, transmission, and scanning electron microscopy. the histological appearance of the tumors was variable; however, 60% were classified as type b adenocarcinomas, while 20% were type a and 20% were composed of equal regions characteristic of both types. four populations of tumor cells were observed with the tem. the most abundant of these, primitive glandular cells, were characterized by large ...19846330878
mouse mammary tumor virus dna methylation: tissue-specific variation.mouse mammary tumor virus-specific dna sequences endogenous to the balb/c mouse are shown to exhibit variable levels of methylation in a tissue-specific manner. in dna from both lactating mammary gland and spleen, mmtv-specific sequences were hypomethylated at specific hpaii and hhai sites. these variably methylated sites were found in the terminal repetitive sequences of the endogenous viral genomes. the specific hypomethylation of a hpaii site in mtv-9 is associated with expression of a 1.6 kb ...19846330997
cellular transforming genes and oncogenesis. 19846331501
different concanavalin a binding patterns of malignant and nonmalignant mouse mammary epithelia in monolayer culture.concanavalin a (con a) binding of fixed malignant and nonmalignant c3h/he mouse mammary epithelia in monolayer cultures was examined with markers and labels of various sizes. in con a-mediated hemadsorption, high epithelial cell densities resulted in the adsorbance of more guinea pig red blood cells per culture dish but fewer per cell. malignant epithelia adsorbed twice as many red blood cells as did nonmalignant cells at the same cell density. ferritin-con a tagged the budding particles of mous ...19846420050
expression of pregnancy-specific genes in preneoplastic mouse mammary tissues from virgin mice.experimentally induced breast cancer is often preceded by the appearance of preneoplastic lesions which possess the attributes of hyperplastic normal tissue. these lesions can be isolated and carried as stably transplantable outgrowth lines which continue to morphologically resemble differentiating mammary tissue (medina, d. methods cancer res., 7: 3-53, 1973). we established seven serially transplantable hyperplastic alveolar nodule (han) outgrowth lines from virgin mouse mammary tissues follow ...19846430550
spontaneous mammary adenocarcinomas in transgenic mice that carry and express mtv/myc fusion genes.we have produced 13 strains of transgenic mice that carry an otherwise normal mouse myc gene in which increasingly larger portions of the myc promoter region have been replaced by a hormonally inducible mouse mammary tumor virus promoter. although expression of the fusion genes varies among these animals, the female founders of two of these transgenic strains spontaneously developed mammary adenocarcinomas during one of their early pregnancies. both the tumors and the breast tissue of these foun ...19846488314
genetic control of pathogenesis of diabetes in c3h mice. influence of the major histocompatibility complex.inbred strains of genetically diabetic (db/db) male mice with h-2b haplotype were heretofore found resistant to the diabetogenic action of the db mutation, whereas c3heb/fej-db/db males with h-2k haplotype were susceptible. to determine whether the major histocompatibility complex was linked to diabetes predisposition, we mated c3h.sw/snj females (h-2b haplotype) with c3heb/fej- +/db males, identified the +/db heterozygotes in the f1 generation (all h-2b/h-2k), and intercrossed these to produce ...19846500186
introduction, stable integration, and controlled expression of a chimeric adenovirus gene whose product is toxic to the recipient human cell.the dna-binding protein (dbp) encoded by human adenoviruses is a multifunctional polypeptide which plays a central role in regulating the expression of the viral genes. to gain a better understanding of the relationships between the various functions provided by dbp, an extensive collection of dbp mutants is essential. to this end we have constructed several permissive human cell lines which contain and express the dbp gene at high levels to allow propagation of otherwise lethal, nonrecoverable ...19846542172
progressive growth of transplanted tumors is accompanied by increasing serum concentrations of murine gamma fetal antigen.balb/c mice bearing growing meth a sarcomas developed gradually increasing serum concentrations of the tumor-associated murine gamma fetal antigen (gamma-fa), a trend which could be reversed by surgical excision of the tumor tissue. this antigen was not detected in the sera of normal adult mice or in the sera of animals with non-neoplastic proliferative condition. although gamma-fa occurs in splenic tissue, its concentration in tumor-bearer serum was unaffected by splenectomy suggesting that gam ...19816795603
using retroviruses as insertional mutagens to identify cellular oncogenes.three criteria have been used to identify cellular genes that might play a role in oncogenesis: (i) homology with known viral transforming genes (v-onc's); (ii) activated expression in tumor cells; and (iii) transforming activity in cultured mouse cells. we have been exploring the hypothesis that retroviruses lacking oncogenes activate cellular oncogenes by insertional mutagenesis. our approach is to locate proviruses within the chromosomal dna of clonal populations of tumor cells, and to identi ...19836867028
effect of thyroid status on development of spontaneous mammary tumors in primiparous c3h mice.development of mammary tumors in primiparous c3h/hen mice (mouse mammary tumor virus positive) in various thyroid states was followed for one year after removal of pups. animals were either euthyroid or made hyperthyroid (by ingestion of thyroxine) or hypothyroid (by ingestion of 2-thiouracil) during involution. these manipulations resulted in significant changes in serum 3,5,3'-triiodo-l-thyronine and thyroxine levels without significant alterations in serum prolactin levels. at the end of one ...19827127296
neoplastic and preneoplastic lesions induced in female c3h mice by diets containing diethylstilbestrol or 17 beta-estradiol.to study the long term effects of estrogenic diets, 2160 virgin female c3h/hel mice, having a high titer to the mammary tumor virus factor (mmtv), were fed diets containing 0, 10, 100, 500, or 1000 ppb diethylstilbestrol (des) or 100, 1000, or 5000 ppb 17 beta-estradiol (e2) from 6 to 110 weeks of age; 1368 virgin female c3heb/fej mice, having a low titer to the mmtv, were fed diets containing 0, 10, 1000, or 500 ppb des from 6 to 136 weeks. in estrogen-treated mice, the incidence of cervical ad ...19807217862
high-level expression of adeno-associated virus (aav) rep78 or rep68 protein is sufficient for infectious-particle formation by a rep-negative aav mutant.adeno-associated virus (aav) codes for four closely related nonstructural proteins (rep) required for aav dna replication and gene regulation. in vitro studies have revealed that either rep78 or rep68 alone is sufficient for aav dna replication. rep52 and rep40 are not required for dna replication but have been reported to enhance the efficiency of accumulation of single-stranded progeny dna. previous studies on rep-expressing cell lines had indicated that only a subset of the four rep proteins ...19957474103
a novel v beta 2-specific endogenous mouse mammary tumor virus which is capable of producing a milk-borne exogenous virus.we have previously reported new mtv loci, mtv-48 and -51, in the japanese laboratory mouse strains cs and nc. here we show by backcross analysis that both mtv-48 and -51 cosegregate with very slow deletion of t cells bearing v beta 2. the nucleotide sequences of the open reading frames in the 3' long terminal repeats of mtv-48 and -51 were very similar to those of mtv-ddo, mouse mammary tumor virus c4 [mmtv(c4)], and mmtv(balb/cv), which encode v beta 2-specific superantigens. furthermore, backc ...19957474151
activation of src family kinases in neu-induced mammary tumors correlates with their association with distinct sets of tyrosine phosphorylated proteins in vivo.overexpression and amplification of the erbb-2 (neu) is thought to play a major role in mammary cancer. although studies suggest that neu is directly involved in the genesis of mammary tumors, the molecular mechanism by which neu induces tumors is not well understood. recently, we have demonstrated that the activity of c-src tyrosine kinase is elevated in neu-induced mammary tumors and this elevated activity correlates with its capacity to physically associate with neu. to explore whether other ...19957478608
role of the tata box in transcription of the mouse mammary tumor virus long terminal repeat.an in vitro transcription system from mammary cells was established to study transcription of the long terminal repeat (ltr) of the mouse mammary tumor virus (mmtv). experiments with progressive 5'-deletion constructs of the mmtv ltr revealed that a 19-base pair (bp) region from -41 to -23 bp, encompassing the tata box and flanking dna sequence, was as transcriptionally active as larger promoter constructs, both in nuclear extracts from human mammary cell lines (t47d and mcf7) and a nonmammary c ...19957491110
glucocorticoid receptor structure and function in an adrenocorticotropin-secreting small cell lung cancer.acth secretion by tumors of nonpituitary origin is characteristically resistant to negative feedback regulation by glucocorticoids. one possible mechanism for the phenomenon could be a structural defect in the intracellular glucocorticoid receptor (gr). we studied the gr in dms-79 cells derived from a human acth-secreting small cell lung cancer. compared with control cells, dms-79 cells were found to have greatly diminished gr ligand-binding activity and immunoreactive 94-kilodalton (kda) gr con ...19957491111
dietary fat: gene expression and mammary tumorigenesis.although discovered as an exogenous agent of mammary carcinoma, the mouse mammary tumor virus (mmtv) is also transmitted vertically as endogenous proviral dna present in the germ line of all inbred mice. in the c3hf mouse, which receives no exogenous virus, the initial event of mammary tumorigenesis is the transcription of the endogenous mmtv proviral dna present at the mtv-1 locus. transcription occurs as a result of the hormonal effects of pregnancy, and mtv-1 specific transcripts are seen in ...19957491294
a redundant nuclear protein binding site contributes to negative regulation of the mouse mammary tumor virus long terminal repeat.the tissue specificity of mouse mammary tumor virus (mmtv) expression is controlled by regulatory elements in the mmtv long terminal repeat (ltr). these regulatory elements include the hormone response element, located approximately between -200 and -75, as well as binding sites for nf-1, oct-1 (otf-1), and mammary gland enhancer factors. naturally occurring mmtv deletion variants isolated from t-cell and kidney tumors, transgenic-mouse experiments with mmtv ltr deletions, and transient transfec ...19957494299
a novel non-mouse mammary tumor virus activation of the int-3 gene in a spontaneous mouse mammary tumor.in a mouse mammary tumor model system in which carcinogenic progression can be investigated, we have found a unique mutation of int-3 associated with progression from premalignant lobular hyperplasia to tumor. sequence analysis of the rearranged fragment revealed an insertion of an intracisternal type a particle (iap) within the int-3 gene. int-3 is mutated frequently in mouse mammary tumor virus (mmtv)-induced mammary tumors by insertion of mmtv proviral dna into this intragenic region. in thes ...19957494323
oncogene activation and oncogene cooperation in mmtv-induced mouse mammary cancer.in this short review, we will give an overview of the various genes that can be activated by insertion of proviral dna of the mouse mammary tumor virus during the formation of mammary cancer. these genes fall within three families: wnt genes, fgf genes and notch-related genes. we will summarize our current understanding of the roles of these genes in tumorigenesis and in normal development, and the mechanisms of action of their gene products. finally, we will give some examples of cooperation be ...19957495980
oct-1 protein promotes functional transcription complex assembly on the mouse mammary tumor virus promoter.the ubiquitous transcription factor oct-1 stimulates basal transcription from the mouse mammary tumor virus (mmtv) promoter by binding to octamer-related sequences present in the proviral long terminal repeat. the mechanism of transcriptional activation by oct-1 was investigated using in vitro transcription assays with a hela cell nuclear extract depleted of endogenous oct-1. oct-1-mediated transcriptional activation could be reconstituted by addition of bacterially expressed recombinant oct-1 p ...19957499253
superantigens: bacterial and viral proteins that manipulate the immune system. 19937506550
activation of the c-src tyrosine kinase is required for the induction of mammary tumors in transgenic mice.transgenic mice expressing the polyomavirus (pyv) middle t oncogene in the mammary epithelium develop multifocal mammary tumors that metastasize with high frequency. the potent transforming activity of pyv middle t antigen can, in part, be attributed to its ability to associate with and to activate a number of c-src family tyrosine kinases (c-src, c-yes, and fyn). as a first step toward assessing the role of individual c-src family tyrosine kinases in pyv middle t antigen-induced mammary tumorig ...19947507074
[derivatives of ddutp, modified at the 5-position of uridine, as substrate terminators of reverse transcriptase. hydrolysis of oligonucleotides, terminated by these analogs, by phosphodiesterase i].synthesis of 2',3'-dideoxyuridine 5'-triphosphate analogues with fluorescent and biotin residues at c5 of uracil base was carried out. the substrate properties of these analogues were studied with amv, m-mlv, and hiv reverse transcriptase. all 5-derivatives studied were shown to be incorporated into the 3'-terminus of oligonucleotide. the stability of oligodeoxyribonucleotides terminated with ddutp analogues modified at the 5-position of the pyrimidine residue to the exonuclease action of phosph ...19947511782
reduction of tumor necrosis factor production by splenocytes from v-ha-ras oncogene-bearing mice.mice containing the activated v-ha-ras oncogene driven by the mouse mammary tumor virus promoter/enhancer produced less tumor necrosis factor (tnf) than genetically identical animals without it. inbred oncomice containing the v-ha-ras oncogene and inbred fvb mice without it were grown for 6 months. splenocytes were isolated and stimulated in vitro to produce tumor necrosis factor (tnf) and gamma-interferon (ifn). tnf production by cells from oncomice was significantly decreased compared to cells ...19937513605
plasmid rescue of an oncogenic sequence containing a mouse mammary tumor virus gene.plasmid rescue was performed on an oncogenically transformed cell line established by transfection of nih/3t3 cells with normal mouse dna and plasmids containing a murine leukemia virus long terminal repeat, and a selectable marker. one of the rescued plasmids contained newly acquired dna 3,500 basepairs in length. this sequence was present in several extra copies in the parental cell line. it was also found to be transcribed. nih/3t3 cells transfected with the rescued plasmid proved to be oncog ...19947517122
whey acidic protein extrinsically expressed from the mouse mammary tumor virus long terminal repeat results in hyperplasia of the coagulation gland epithelium and impaired mammary development.the whey acidic protein (wap) is a milk protein that contains a cysteine-rich motif. this characteristic wap signature has also been found in some protease inhibitors and certain proteins involved in tissue modeling. wap is specifically synthesized in mammary tissue from late pregnant and lactating animals, and precocious synthesis results in impaired lobuloalveolar development of the gland in some transgenic lines. to determine whether growth modulatory effects of wap are confined to mammary ti ...19947522033
igf-i-induced igfbp-3 potentiates the mitogenic actions of igf-i in mammary epithelial md-igf-i cells.limited information is available concerning the molecular and cellular mechanisms that regulate expression of insulin-like growth factor-i (igf-i) binding proteins (igfbps) in bovine mammary epithelial cells. here, we report on the autocrine mechanisms of action of igf-i and hormonal regulation of expression of igfbps in bovine mammary epithelial md-igf-i cells which express recombinant igf-i under the control of the glucocorticoid-inducible mouse mammary tumor virus-long terminal repeat (mmtv-l ...19947523204
reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: implications for superantigen function.mouse mammary tumor virus (mmtv) encodes a superantigen (sag) that promotes stable infection and virus transmission. upon subcutaneous mmtv injection, infected b cells present sag to sag-reactive t cells leading to a strong local immune response in the draining lymph node (ln) that peaks after 6 d. we have used the reverse transcriptase inhibitor 3'-azido-3'-deoxythymidine (azt) to dissect in more detail the mechanism of sag-dependent enhancement of mmtv infection in this system. our data show t ...19947525852
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