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maternal transfer of infectious mouse mammary tumor retroviruses does not depend on clonal deletion of superantigen-reactive v beta 14+ t cells.female c3h/hej mice maternally transmit through their milk an infectious mouse mammary tumor retrovirus (mmtv) which causes clonal deletion of t cell receptor (tcr)v beta 14+ t cells reactive to the retroviral superantigen (sag). to test whether cd4+ or cd8+ t cells are crucial for intestinal infection and maternal transfer of exogenous retroviruses, newborn mice lacking cd4 or cd8 molecules after gene targetting were raised by surrogate c3h/hej mothers. in cd8-/- mice, clonal deletion of tcrv b ...19948181521
mammary tumorigenesis and metastasis in transgenic mice.the transgenic mouse has emerged as an important model system to assess the transforming potential of oncogenes in the mammary epithelium. mammary gland-specific expression of oncogenes in transgenic mice has resulted in the induction of a variety of phenotypes ranging from benign epithelial hyperplasias to metastatic mammary tumors. the induction of tumors in most of these transgenic models is a multi-step process where transgene expression, although required, is not sufficient for conversion o ...19948186390
the impact of 5'-cg-3' methylation on the activity of different eukaryotic promoters: a comparative study.the inhibiting or inactivating effects of position-specific promoter methylation in different viral or human cellular promoters ad2 e2al, sv40, ltr-mmtv, hsv-tk, tnf alpha) have been compared by in vitro 5'-ccgg-3' methylation by m-hpaii or the m-sssi dna-methyltransferase, respectively. in most promoters, 5'-cg-3' methylation reduces activity to a few percent of that of mock-methylated controls. the number of 5'-cg-3' dinucleotides in a promoter does not strictly correlate with the extent of me ...19948187893
two glucose-signaling pathways in s14 gene transcription in primary hepatocytes: a common role of protein phosphorylation.transcription of the rat s14 gene is induced in response to increased carbohydrate metabolism in the liver. because carbohydrate-induced changes in lipogenesis are mediated in part by changes in phosphorylation of multiple proteins, we investigated the role of protein phosphorylation on transcriptional regulation of the two carbohydrate response elements, a thyroid hormone receptor-independent carbohydrate response element and a thyroid receptor-dependent glucose response element located up-stre ...19948194479
superantigens and retroviral infection: insights from mouse mammary tumor virus.superantigens induce a vigorous immune response by stimulating t cells that express particular t-cell receptor v beta chains. mouse mammary tumor virus is a milk-transmitted retrovirus that encodes such a superantigen. paradoxically, as discussed by werner held and colleagues, the strong superantigen-induced immune response permits the survival of the virus via t-cell dependent clonal expansion of infected b cells.19948198710
on the generation of diversity in endogenous superantigens. 19948198711
[superantigens]. 19948202838
mammary hyperplasia and carcinoma in mmtv-cyclin d1 transgenic mice.physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control. cyclin d1 was identified as a candidate oncogene (prad1) in tumour-specific dna rearrangements and is suspected to be a contributor to several types of neoplasms including breast cancer. cyclin d1 also rescues g1 cyclin-defective saccharomyces cerevisiae, and is a growth-regulated gene. despite evidence suggesting that cyclin d1 is an oncogene, its ability to tra ...19948208295
transcription of multiple exogenous mouse mammary tumor viruses in a single mammary tumor of an shn mouse.the shn mouse strain, established in japan independently from other mammary tumor-prone strains, is known to have a very high incidence of early-onset mammary tumors. in this study, we demonstrate that exogenous mouse mammary tumor virus (mmtv) plays a crucial role in early-onset mammary tumorigenesis in this strain. we subsequently isolated mmtv rna from a mammary tumor of an shn female mouse, reverse transcribed it, and amplified a 1.2-kb coding region of the long terminal repeat (ltr) by use ...19947898031
mammary tumors expressing the neu proto-oncogene possess elevated c-src tyrosine kinase activity.amplification and overexpression of the neu (c-erbb2) proto-oncogene has been implicated in the pathogenesis of 20 to 30% of human breast cancers. although the activation of neu receptor tyrosine kinase appears to be a pivotal step during mammary tumorigenesis, the mechanism by which neu signals cell proliferation is unclear. molecules bearing a domain shared by the c-src proto-oncogene (src homology 2) are thought to be involved in signal transduction from activated receptor tyrosine kinases su ...19947903421
superantigens produced by infectious pathogens: molecular mechanism of action and biological significance."superantigens" have in common an extremely potent stimulatory activity for cd4+, cd8+, and some gamma delta+ t lymphocytes. superantigens use a unique mechanism: they crosslink variable parts of the t cell receptor with mhc class ii molecules on accessory or target cells. the interaction site on the t cell receptor is the variable part of the beta-chain (v beta). there are several reasons why these molecules have aroused such tremendous interest in recent years. first, they have provided key in ...19947894042
androgens regulate expression of the gene coding for a mouse vas deferens protein related to the aldo-keto reductase superfamily in epithelial cell subcultures.mouse vas deferens protein (mvdp), a member of the aldo-keto reductase superfamily, is exclusively produced in the vas deferens. to better understand androgen-regulated mvdp gene expression we have used rna hybridization to study the effects of androgens on the steady-state levels of mvdp mrna in vas deferens epithelial cell subcultures. northern blot analysis revealed that these cells only express mvdp mrna in the presence of androgens. there was a close relationship between mvdp mrna levels an ...19948136297
activation of natural killer cells by mouse mammary tumor virus c4 in balb/c and t-cell receptor v beta 2-transgenic mice.lymphocytic infiltrates of balb/c c4 hyperplastic alveolar nodule (han) have elevated natural killer (nk) activity, which correlates positively with the progression of c4 han to tumor: c4 han produces an infectious mouse mammary tumor virus, mmtv(c4), which encodes a superantigen that activates and deletes t-cells with the v beta 2 segment in the t-cell receptor. in this report, nk activation by both mmtv(c4) and mmtv(c4) superantigen was tested. nk activity was measured in naive balb/c mice, ba ...19948137259
acceleration of mammary neoplasia in transforming growth factor alpha transgenic mice by 7,12-dimethylbenzanthracene.a mouse mammary tumor virus enhancer/promoter-transforming growth factor alpha transgenic mouse model has been described in which mammary tumors develop (y. matsui et al., cell, 61: 1147-1155, 1990). in line 29, spontaneous mammary tumors do not develop before 300 days of age in virgin females. herein, line 29 virgin females and their nontransgenic littermates have been treated with 7,12-dimethylbenzanthracene (dmba) at varying dosages and times. orogastric instillation of a single dose of dmba ...19948137281
expression and purification of the mouse mammary tumor virus gag-pro transframe protein p30 and characterization of its dutpase activity.the mouse mammary tumor virus gag-pro transframe protein (p30) contains the nucleocapsid protein domain derived from the 3' end of gag, fused to 154 residues encoded by the 5' region of the pro open reading frame. the dna coding for p30 was cloned into the plasmid palter-1, and an additional nucleotide was inserted by site-directed mutagenesis to allow the read-through from the gag into the pro open reading frame. the obtained insert was then cloned into pgex-2t, a plasmid containing the glutath ...19948139016
levels of viral glycoprotein reflect enhanced effectiveness of combined drug treatments.a chemosensitivity assay with small replicate mm5mt/cl c3h mammary tumor cell cultures was developed to determine whether changes in viral antigen expression and release into culture fluids could be utilized as an in vitro measure of single and combined drug effect. the measurement of drug concentrations required for identical 50% reductions in viral antigen levels (ed50s) allowed the dosage-dependence of the same drug to be compared alone and in combination drug treatments. the 52,000 mw viral ...19948139377
potentiation of glucocorticoid-mediated induction of the mouse mammary tumor virus promoter in mammary carcinoma cells by activation of protein kinase c.in a mammary carcinoma cell line, the glucocorticoid induction of a stably integrated mouse mammary tumor virus-luciferase reporter gene is potentiated up to ten-fold by treatment of the cells with phorbol ester tumor promoters. this potentiation is stereospecific and is observed with a structurally unrelated tumor promoter that also activates protein kinase c. another tumor promoter, thapsigargin, that acts via mobilization of intracellular calcium stores, fails to potentiate the hormone respon ...19948117276
identification of two v beta 7-specific viral superantigens.the commonly used strains of laboratory mice have mouse mammary tumor viruses (mtv) integrated at various locations in their dna. the number and position of these integrants varies from one strain of mouse to another. it has recently been shown that the genomes of many of the mtv code for superantigens. the predicted amino acid sequences of these superantigens and their specificity for tcr v beta differs for each mtv integrant. this study contains the predicted amino acid sequence and v beta spe ...19948254207
a v beta 8.2-specific superantigen from exogenous mouse mammary tumor virus carried by fm mice.a number of endogenous mouse mammary tumor virus (mmtv) proviruses encode superantigen that have the ability to stimulate t cells with a certain t cell receptor (tcr) beta-chain variable region (v beta) and to mediate the v beta-specific clonal deletion. the tumorigenic milk-borne mmtv carried by c3h and gr mice also have superantigenic properties in vivo. in the present study we identified and characterized a novel v beta 8.2-specific superantigen of exogenous mmtv carried by fm mice. the open ...19947913038
transmission of an mls-1a-like superantigen to balb/c mice by foster-nursing on f1 mls-1bxa mothers. sex-influenced onset of clonal deletion.foster nursing of balb/c (mls-1b) mice on (balb/cxakr/j)f1 and (balb/cxdba/2)f1 (mls-1bxa), but not on (balb/cxc57bl/6)f1 or (balb/cxc3h/he)f1 (mls-1bxb mothers, induced the progressive deletion of v beta 6+ and v beta 8.1+ t cells in 50% of the litter. the onset of this mls-1a-like clonal deletion was markedly sex-influenced, being earlier in females (8-10 wk of age) than in males (32 wk). in both sexes, cd4+ v beta 6+ cells were more affected than cd8+ v beta 6+ cells. decreases in the percent ...19947913941
dimerization characteristics of the dna- and steroid-binding domains of the androgen receptor.the dna-binding domain (dbd) of the androgen, mineralocorticoid, and glucocorticoid receptors and the steroid-binding domain (sbd) of the androgen receptor (ar) were expressed separately as fusion proteins with glutathione-s-transferase (gst) in escherichia coli. native polyacrylamide gel electrophoresis and gel exclusion hplc demonstrated that the gst-ardbd fusion protein was present as a dimer. on the other hand, the gst-arsbd fusion protein formed a high-molecular weight oligomer, which seeme ...19947918108
mouse mammary tumor virus superantigens and murine autoimmune gastritis.neonatal thymectomy induces autoimmune gastritis in balb/c (minor lymphocyte-stimulating antigen [mls]-1b) mice, whereas dba/2 (mls-1a) mice are resistant. resistance has been linked to the mls-1a locus, which encodes a retroviral superantigen, and to superantigen reactive t cells that express v beta 6+ t-cell receptors. v beta 6+ t cells are known to be deleted in mice expressing mls-1a superantigens.19947926482
conditional expression of human tnf-alpha: a system for inducible cytotoxicity.tumour necrosis factor-alpha (tnf-alpha) is currently being used in clinical trials for cancer treatment, but toxic side effects, due to systemic administration and high doses, are observed. inducible expression of tnf may permit selective killing of tumour cells in gene therapy protocols without need for prolonged and/or high-level tnf expression. a conditional tnf expression vector has been constructed in which the coding sequences of human tnf have been placed under the transcriptional contro ...19947927889
regulation of the mouse mammary tumor virus receptor by phosphorylation and internalization in mammary epithelial cells.the mouse mammary tumor virus enters mammary epithelial cells via a plasma membrane protein that binds to a viral envelope glycoprotein, gp52. in intact cells, this gp52 receptor can be phosphorylated by activators of protein kinase a and protein kinase c (pkc), but this modification does not occur in response to epidermal growth factor, whose receptor is a tyrosine kinase, or to gp52. phosphorylation of the gp52 receptor rapidly leads to internalization and gradual loss of binding activity. bot ...19947929597
retroviral infection of neonatal peyer's patch lymphocytes: the mouse mammary tumor virus model.mouse mammary tumor virus is known to infect newborn mice via mother's milk. a proposed key step for viral spread to the mammary gland is by the infection of lymphocytes. we show here that although in suckling mice retroviral proteins are found in all epithelial cells of the gut, viral dna is exclusively detectable in the peyer's patches. as early as 5 d after birth the infection leads to a superantigen response in the peyer's patches but not in other lymphoid organs draining the intestine. vira ...19947931081
cell lines inducibly expressing the adeno-associated virus (aav) rep gene: requirements for productive replication of rep-negative aav mutants.the adeno-associated virus (aav) rep gene codes for a family of nonstructural proteins which are required for aav gene regulation and dna replication. in addition, rep has been implicated in a variety of activities outside the aav life cycle which have been difficult to study, since attempts to achieve separate and constitutive expression of rep in stable cell lines have failed so far. here we report the generation of two cell lines which inducibly express rep78 under the control of the glucocor ...19947933099
novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors.amplification of the neu/c-erbb-2 receptor tyrosine kinase has been implicated as an important event in the genesis of human breast cancer. indeed, transgenic mice bearing either an activated form of neu or the wild-type proto-oncogene under the transcriptional control of the mouse mammary tumor virus promoter-enhancer frequently develop mammary carcinomas (l. bouchard, l. lamarre, p. j. tremblay, and p. jolicoeur, cell 57:931-936, 1989; c. t. guy, m. a. webster, m. schaller, t. j. parson, r. d. ...19947935422
detection of transcription factor binding in vivo using lambda exonuclease. 19947937164
relative glucocorticoid potency revisited.to determine the relative potency of synthetic glucocorticoids, glucocorticoid receptor expressing cells were transfected with a hormone-inducible reporter gene, and were cultured in the presence of various glucocorticoid ligands. hormonal inducibility was determined by means of a chloramphenicol acetyltransferase assay. dexamethasone and prednisolone, as well as cortisol, induced the expression of the reporter gene in a dose-dependent fashion. the relative potency of each ligand was in this ord ...19947939139
genome organization of a biologically active molecular clone of the lymphoproliferative disease virus of turkeys.the lymphoproliferative disease retrovirus (lpdv) induces an acute, horizontally transmitted disease of turkeys that is often fatal. although lpdv cannot be grown in cultured cells, it was possible to isolate molecular clones of biologically active integrated proviral genomes from spleens of infected turkeys. based upon molecular hybridization and nucleotide sequence comparisons of its pol gene, lpdv was shown to represent a distinct group of avian retroviruses most closely related to avian sarc ...19947941337
11 beta-hydroxysteroid dehydrogenase activity in human lung cells and transcription regulation by glucocorticoids.selectivity to aldosterone (aldo) in mineralocorticoid target tissues has been suggested to be due to the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-hsd). this enzyme inactivates the endogenous glucocorticoid cortisol, thus permitting the unhindered access of aldo to the mineralocorticoid receptor. the 11 beta-hsd activity was measured by the conversion of cortisol to cortisone and vice versa. concomitant treatment of the cells with either cortisone or cortisol in the presence of ...19947943349
two independent pathways for transcription from the mmtv promoter.the influence of progesterone receptor (pr) and glucocorticoid receptor (gr) on transcription from the mouse mammary tumour virus (mmtv) promoter was analyzed using cell-free transcription of dna templates with a g-free cassette. preincubation of the templates with either pr or gr stimulates the rate of transcription initiation 10-50 fold, whereas the recombinant dna binding domain of gr is inactive. mutations that inactivate the nuclear factor i (nfi) binding site, or nfi depletion of the nucle ...19947947347
transcription activation of mouse mammary tumor virus-chloramphenicol acetyltransferase: a model to study the metabolism of cortisol.the human 11 beta-hydroxysteroid dehydrogenase (h11 beta-hsd) inactivates the active corticosteroid cortisol to its inactive metabolite cortisone. we have developed transactivation analyses of the reporter chimeric gene mouse mammary tumor virus-chloramphenicol acetyltransferase (mmtv-cat) to study the catalytic activity of h11 beta-hsd introduced by cotransfection into receptor and 11 beta-hsd deficient cv-1 cells. assay of 11 beta-hsd expressed in cv-1 cells by cotransfection showed that the c ...19947947689
the establishment of the long terminal repeat of the mouse mammary tumor virus into cv-1 cells allows a functional analysis of steroid receptors.to analyze in situ the effects of mineralocorticoid receptor (mr) on the nucleo-protein organization of the target mmtv promoter, we have established a new cell line by integrating in cv-1 cells a construct containing the long terminal repeat of the mouse mammary tumor virus (mmtv-ltr). the mmtv-ltr contains glucocorticoid response elements (gres), known to interact with mr. cv-1 cells were selected because they lack glucocorticoid receptor (gr). the absence of gr in the host cell line allows th ...19947948018
the androgen receptor in the testicular feminized (tfm) mouse may be a product of internal translation initiation.androgen insensitivity in the testicular feminized (tfm) mouse is caused by frame-shift mutation in the androgen receptor (ar) mrna, which results in a stop codon in the amino terminus. despite this mutation, a smaller sized protein corresponding to the dna- and steroid-binding domain of the ar can be synthesized from the cloned tfm ar cdna by in vitro translation. the tfm ar construct was demonstrated to express a protein capable of binding androgen with an affinity similar to the cloned wild-t ...19947950980
homologous down-regulation of the glucocorticoid receptor down-modulates cellular hormone responsiveness in human histiocytic lymphoma u937 cells.one of the determinants of cellular responsiveness to glucocorticoid hormone is the concentration of the receptor protein. it is well-known that cellular receptor levels are down-regulated by the cognate ligands, but the biological significance of this homologous down-regulation of the receptor has not yet been completely understood. we showed that in human histiocytic lymphoma cell line u937 the cellular glucorticoid receptor was homologously down-regulated by means of both ligand binding and w ...19947704085
rat t cell response to superantigens. i. v beta-restricted clonal deletion of rat t cells differentiating in rat-->mouse chimeras.t cells of mice display v beta-specific reactivity for a spectrum of mouse mammary tumor virus (mtv) antigens; confrontation with these antigens during ontogeny causes substantial "holes" in the t cell repertoire. since endogenous mtv antigens are rare in other species, the question arises whether v beta-specific recognition of mtv antigens is unique to mice. to examine this question, rat t cells were allowed to differentiate from stem cells in severe combined immunodeficiency (scid) mice. these ...19948270883
rat t cell responses to superantigens. ii. allelic differences in v beta 8.2 and v beta 8.5 beta chains determine responsiveness to staphylococcal enterotoxin b and mouse mammary tumor virus-encoded products.the previous paper in this series demonstrates that rat t cells developing de novo in the presence of mouse mammary tumor virus (mtv) antigens in rat-->severe combined immunodeficiency (scid) mouse xenochimeras display a distinct pattern of v beta-restricted deletion; this deletion pattern is remarkably similar to that occurring during thymic development of mouse t cells in mtv+ strains. in addition, t cells developing in the absence of mtv antigens in these rat-->mouse xenochimeras are tolerant ...19948270884
nucleosome-mediated disruption of transcription factor-chromatin initiation complexes at the mouse mammary tumor virus long terminal repeat in vivo.glucocorticoid induction of mouse mammary tumor virus (mmtv) is short lived, returning to base levels within 24 h despite the continued presence of hormone. mmtv dna sequences assembled as chromatin require hormone for binding by nuclear factor 1 (nf1) and octamer proteins (oct). however, in the same cells, nf1 and oct factors are bound to transiently introduced dna in the absence of hormone. in contrast, recruitment of the tata-binding protein and a novel dna-binding protein, which we have desi ...19948264599
preferential repair of uv damage in highly transcribed dna diminishes uv-induced intrachromosomal recombination in mammalian cells.the relationships among transcription, recombination, dna damage, and repair in mammalian cells were investigated. we monitored the effects of transcription on uv-induced intrachromosomal recombination between neomycin repeats including a promoterless allele and an inducible heteroallele regulated by the mouse mammary tumor virus promoter. although transcription and uv light separately stimulated recombination, increasing transcription levels reduced uv-induced recombination. preferential repair ...19948264606
repression of mouse mammary tumor virus transcription by a transcription factor complex. binding of individual components to separated dna strands.expression of mouse mammary tumor virus in t lymphocytes appears to be required for accession of horizontally transmitted virus to the mammary gland. further, deletions in the long terminal repeat which relax constraints on viral transcription promote t cell lymphoma. we have identified a polypurine transcriptional repressor element (nre1) that is deleted from viruses that induce t cell lymphoma. nre1 binding activity in nuclear extracts proved to be related to a growth inhibitory activity that ...19948288611
stably integrated mouse mammary tumor virus long terminal repeat dna requires the octamer motifs for basal promoter activity.in the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized by ubiquitous and tissue-restricted oct transcription factors, is located upstream of the tata box and next to a binding site for the transcription factor nuclear factor i (nf-i). their function was investigated with mutant long terminal repeats under different transfection conditions in mouse ltk- cells and quantitative s1 nuclease mapping of the transcripts. in stable transfectants, which are most representative ...19948289800
physical association and functional antagonism between the p65 subunit of transcription factor nf-kappa b and the glucocorticoid receptor.glucocorticoids, which are widely used as antiinflammatory agents, downregulate the expression of the interleukin 6 gene and of additional cytokine genes involved in inflammatory responses. conversely, the transcription factor nf-kappa b, a member of the rel family of transcription factors, has been implicated in the induction of multiple genes involved in the early processes of immune and inflammatory responses. this prompted us to investigate whether one of the mechanisms by which glucocortico ...19948290595
the mouse mammary tumor virus envelope gene product is required for superantigen presentation to t cells.transgenic mice expressing either the mouse mammary tumor virus (mmtv) superantigen gene (sag) alone or in combination with the viral envelope genes (env) (lel), or all of the viral genes (gag, pol, env, and sag) (hyb pro), deleted v beta 14+ t cells from their immune repertoire. however, only lel or hyb pro transgenic antigen-presenting cells were capable of stimulating a proliferative response from nontransgenic primary t cells or interleukin 2 production from a v beta 15-bearing t cell hybrid ...19948294859
delay in expression of a mammary tumor provirus is responsible for defective clonal deletion during postnatal period.a gene-encoding ligand for deletion of t cells bearing tcrv beta 6 and v beta 8.1 cosegregates a new mammary tumor provirus locus, mtv-50 in nc mice. the sequence of the open reading frame (orf) in the 3' long terminal repeat (ltr) of mtv-50 was strikingly similar to those of mtv-7, mtv-43 and exogenous mouse mammary tumor virus (sw) with properties of minor lymphocyte stimulating antigen 1a. consistent with previous reports, clonal deletion of mature thymocytes bearing tcrv beta 6 was defective ...19948299700
tissue-specific expression of messenger rnas encoding endogenous viral superantigens.the minor lymphocyte stimulating (mls) superantigens of mice are encoded by open reading frames (orfs) in the 3' long terminal repeats (ltrs) of endogenous mouse mammary tumor viruses. by stimulating all t cells bearing particular tcr v beta proteins, these viral superantigens (v-sags) exert profound effects on t cell development and function. we have examined expression of the 1.7 kb mrna product predicted to encode v-sag proteins in different cells and tissues of the immune system. the ltr-orf ...19948301115
expression of mtv-7 sag gene in vivo using a retroviral vector results in selective inactivation of superantigen reactive t cells.t cells expressing specific tcr v beta chains are intrathymically eliminated in mice expressing the murine mls (minor lymphocyte stimulating) superantigens. recently, in vitro studies have shown that the endogenous mouse mammary tumor virus (mmtv)-7 sag gene encodes mls-1 ag. the demonstrated ability of mmtv superantigen proteins to react with tcrs has led to the postulate that other infectious retroviruses may use superantigen-like molecules to modify the host's immune system. in this report, s ...19948301116
exogenous mtv-7 superantigen transgene expression in major histocompatibility complex class ii i-e- mice reconstituted with embryonic stem cell-derived hematopoietic stem cells.direct genetic manipulation of hematopoietic cells is limited by the lack of an established hematopoietic stem cell line. it has been demonstrated that embryonic stem (es) cell<-->tetraploid embryos are completely es cell-derived and that fetal liver (fl) cells from these embryos support hematopoiesis in lethally irradiated recipients. in this report, we demonstrate that fl cells from es cell<-->tetraploid embryos support normal lymphopoiesis and t-cell repertoire development. moreover, the intr ...19948302843
effect of vitreoscilla hemoglobin expression on growth and specific tissue plasminogen activator productivity in recombinant chinese hamster ovary cells.previous studies suggest that secretion of cloned proteins synthesized by recombinant chinese hamster ovary (cho) cells can be adenosine triphosphate (atp) limited. other research indicates that the presence of cloned vitreoscilla hemoglobin (vhb) enhances atp production in oxygen-limited escherichia coli. to evaluate the influence of vhb expression on recombinant cho cell productivity, the vhb gene has been fused to the mouse mammary tumor virus (mmtv) promoter and cloned in a cho cell line pre ...199418618650
mouse mammary tumor virus proviral integration in the dd/tbr mice.the patterns of mouse mammary tumor virus (mmtv) integration in the dna of spontaneous-mammary tumors, salivary glands and livers of dd/tbr mice were examined using mmtv env, int -1c and int-2c probes. the mmtv env probe revealed 1 to 7 new proviral insertions in all mammary tumors. mmtv integration into int-1 was observed in 10 of 18 mammary tumors, whereas that into int-2 was seen in only 2 of 18 tumors. of the 13 salivary glands examined, only 3 showed new mmtv proviral integrations, but rear ...199411091502
complete nucleotide sequence of mouse mammary tumor virus from jyg chinese wild mice: absence of bacterial insertion sequences in the cloned viral gag gene.mammary tumors of a newly isolated strain of chinese wild mouse (jyg mouse) harbor exogenous mouse mammary tumor virus (mmtv). the complete nucleotide sequence of exogenous jyg-mmtv was determined on the proviral 5' long terminal repeat (ltr)(partial)-gag-pol-env-3' ltr (partial) fragment cloned into a plasmid vector and the cdna sequence from jyg-mmtv producing cells. similarly to the other mmtv species the ltr of jyg-mmtv contains an open reading frame (orf). the amino acid sequence of the jyg ...199411091515
transgenic animals and the study of cancer.this chapter seeks to outline the strategies being employed to exploit transgenic mice as a tool in the study of cancer. rather than catalog the many different oncogene and oncogene-promoter combinations that have been introduced into transgenic mice to elicit tumors, i will concentrate on a single system that epitomizes the general approach. that system, pioneered by philip leder of harvard university, is mammary carcinogenesis induced by oncogene expression directed by the mouse mammary tumor ...199321390643
mls-1 and mls-2 superantigens do not control susceptibility to collagen-induced arthritis in hi and hii mice.the hi mouse line is sensitive to collagen-induced arthritis (cia), whereas hii is refractory, although both express the h-2q permissive haplotype. the two lines also share the same t-cell receptor (tcr) gene haplotypes for alpha and beta chains. the distribution of mouse mammary tumour viruses (mmtv), which encode endogenous superantigens (sag) such as minor leucocyte-stimulating antigens (mls) known to modulate the available tcr-v beta repertoire, was investigated in the two lines. mls-1 is pr ...19938307618
mvm(p) ns-2 protein expression is required with ns-1 for maximal cytotoxicity in human transformed cells.the parvovirus-encoded nonstructural (ns) proteins have been implicated in the cytopathogenicity of these agents. although protein ns-1 of minute virus of mice (mvm) has been shown to be toxic, little is known about the role of ns-2 in this process. in order to determine the contribution of ns-1 and ns-2 to cytotoxicity, we took advantage of an expression system controlled by the mouse mammary tumor virus promoter which responds to glucocorticoid stimulation and which controls the expression of ...19938317090
superantigens as immunogens and tolerogens.superantigens are a family of proteins that are receiving a great deal of attention as a group of potent immunomodulatory molecules. they combine with mhc class ii molecules to form the ligands that stimulate t cells via the v beta element of the t cell receptor. two groups of superantigens have been described: those expressed endogenously such as the mouse mammary tumour virus (mmtv) and the exogenously derived products such as the staphylococcal enterotoxins. here we review the interactions be ...19938324944
the steroid antagonist ru486 exerts different effects on the glucocorticoid and progesterone receptors.to determine whether the steroid antagonist ru486 mediates its antiglucocorticoid and antiprogestin activities by the same or different receptor mechanisms, a direct comparison of ru486 interaction with glucocorticoid (gr) and progesterone (pr) receptors was made. the effects of ru486 on transformation of gr and pr 8-10s complexes in the intact cell and in vitro were analyzed by sucrose density gradient centrifugation, and the in vitro stability of receptor-heat shock protein-90 interactions was ...19938344212
differential regulation of human progesterone receptor a and b form-mediated trans-activation by phosphorylation.hormone-dependent phosphorylation of progesterone receptors (prs) plays a functional role in their transcriptional activity. however, hormone-independent phosphorylation has also been shown to modulate the chicken pr-mediated trans-activation in the presence of phosphorylating agents. the present study was designed to investigate the effects of protein kinase a- and protein kinase c-mediated signal transduction pathways on the regulation of the activity of the two forms of human pr (hpra and hpr ...19938365365
moloney murine leukemia virus protease: bacterial expression and characterization of the purified enzyme.the moloney murine leukemia virus (mo-mulv) protease has been cloned into the prokaryotic expression vector pgex-2t, expressed in fusion with the glutathione s-transferase from schistosoma japonicum, and purified to apparent homogeneity after thrombin cleavage of the chimeric protein. the purified protease showed maximum activity at ph 6.0 and was inhibited by several aspartyl protease inhibitors, found to be active toward the human immunodeficiency virus-1 (hiv-1) protease. peptides representin ...19938372434
a mouse mammary tumor virus promoter element near the transcription initiation site.transcription from the promoter of mouse mammary tumor virus is subject to both positive and negative control by cellular factors, and proviral promoter elements that mediate a basal level of transcription must in some way respond to these cellular regulatory signals. several such elements, including a tata box, a region containing three octamer-related sequences, and a binding site for nuclear factor 1, have been previously defined. additional promoter mutations have allowed a fourth basal prom ...19938380087
mhc class ii limits the functional expression of endogenous superantigens in b cells.the open reading frames of the 3' long terminal repeat of mouse mammary tumor viruses (mmtv) encode superantigens. when expressed with mhc class ii molecules on the surface of b cells, superantigens stimulate t cells expressing receptors with particular v beta elements. by using b cell lymphomas as model systems, we demonstrate that stimuli, including certain lymphokines (il-2 and il-5) and lps, that lead to increased mmtv transcript levels in b cells did not increase functional superantigen pre ...19938380190
steroid hormone dependent changes in dna methylation and its significance for the activation or silencing of specific genes. 19938380354
regulation of expression of mouse mammary tumor virus through sequences located in the hormone response element: involvement of cell-cell contact and a negative regulatory factor.mouse mammary tumor virus (mmtv) is a latently oncogenic retrovirus responsible for the neoplastic transformation of mammary epithelial cells. its expression is regulated by steroids, polypeptide growth factors, and cell-type-specific factors. using gr mouse mammary cells and nih 3t3 fibroblasts stably transfected with chimeric constructs of the long terminal repeat region of mmtv, we have demonstrated a novel mechanism of cell-type-specific expression of this virus. in confluent monolayer cultu ...19938380466
t-cell receptor b-v repertoire expression in the absence of an endogenous mouse mammary tumor provirus. 19938380566
the glucocorticoid receptor and a putative repressor protein coordinately modulate glucocorticoid responsiveness of the mouse mammary tumor virus promoter in the rat hepatoma cell line m1.19.signal transduction by glucocorticoid hormones is mediated by the intracellular glucocorticoid receptor protein. the mechanisms determining cell type- or tissue-specific differences in hormone responsiveness remain, however, unclear. to address this issue we have used two different rat hepatoma cell lines, 762 and 6.10.2, respectively, in which mouse mammary tumor virus has been stably integrated. nuclear extracts from both of these cell lines contained a factor that bound to a sequence motif ex ...19938380580
mouse mammary tumor virus infection accelerates mammary carcinogenesis in wnt-1 transgenic mice by insertional activation of int-2/fgf-3 and hst/fgf-4.transgenic mice carrying the wnt-1 protooncogene modified for expression in mammary epithelial cells exhibit hyperplastic mammary glands and stochastically develop mammary carcinomas, suggesting that additional events are necessary for tumorigenesis. to induce such events and to identify the genes involved, we have infected wnt-1 transgenic mice with mouse mammary tumor virus (mmtv), intending to insertionally activate, and thereby molecularly tag, cooperating protooncogenes. infection of breedi ...19938380647
production and characterization of an mls-1-specific monoclonal antibody.superantigens (sags) represent a new class of antigens, characterized as t cell receptor (tcr) v beta-reactive elements. bacterial toxins constitute the major group of exogenous sags, while the mouse mammary tumor virus (mmtv)-encoded mls molecules represent the endogenous sags. mls-1 is the prototype of the latter sags, because it elicits a very potent t cell stimulatory response in vitro in unprimed t cells expressing the tcr v beta 6 or 8.1 chains. in vivo, mls-1 causes deletion of immature t ...19938381154
major histocompatibility complex-specific recognition of mls-1 is mediated by multiple elements of the t cell receptor.we have recently shown that recognition of the mouse mammary tumor virus 9-associated superantigen (vsag-9) by murine v beta 17+ t cells is strongly influenced by the major histocompatibility complex (mhc) class ii haplotype of the presenting cells, resulting in a form of mhc-restricted recognition. this finding was unexpected, because t cell recognition of another well-characterized retroviral superantigen, minor lymphocyte-stimulating antigen 1 (mls-1), had been shown to be independent of the ...19938381156
a gene encoding the ligand for deletion of t cells bearing tcrv beta 6 and v beta 8.1 cosegregates with a new endogenous mouse mammary tumor virus. 19938381390
trafficking of wild-type and an endoproteolytic-site mutant of the mouse mammary tumor virus glycoprotein.we have utilized a mouse mammary tumor virus (mmtv) glycoprotein gene containing a mutation in the endoproteolytic cleavage site to investigate the biological significance of processing, the structural requirements for and the events involved in the proteolytic maturation of mmtv. using oligonucleotide-directed mutagenesis, the endoproteolytic cleavage site within the mmtv glycoprotein was mutated from arg-ala-lys-arg to arg-ala-asn-gln and both the wild-type and mutated genes were transfected a ...19938381404
phylogenetic and structural analyses of mmtv ltr orf sequences of exogenous and endogenous origins.the long terminal repeat (ltr) of mouse mammary tumor virus (mmtv) harbors an open reading frame (orf) that encodes a glycoprotein and is present in all exogenous and endogenous mmtv proviruses. the orf protein has been reported to interact with the immune system of mice to cause deletion of specific v beta-bearing subsets of t cells. twenty-two mmtv ltr orf sequences were analyzed. although highly conserved, the mmtv orf sequences are not identical, with approximately 35% of the total variation ...19938382394
calories, parity, and prolactin influence mammary epithelial kinetics and differentiation and alter mouse mammary tumor risk.reduced calorie intake (rci) suppresses mouse mammary tumor virus (mmtv) transcription and reduces mammary tumor (mt) incidence in c3h/ou mice. since efficient retroviral expression requires cell division, we investigated whether the suppression of mmtv and mt by rci reflects changes in mammary histogenesis and lowered epithelial kinetics. prolactin (prl) augments mmtv transcription. since prl levels may be lowered by rci, we evaluated whether lowered prl in ad libitum-fed mice alters mammary hi ...19938382558
synergistic induction of apoptosis with glucocorticoids and 3',5'-cyclic adenosine monophosphate reveals agonist activity by ru 486.glucocorticoids induce a programmed cell death in immature murine t cells through a process that has been named apoptosis. cyclic amp-dependent protein kinase (pka) activity contributes to this response but acts through an undefined mechanism. steroid-induced cytolysis can be completely blocked by the glucocorticoid antagonist ru 486, which inhibits the transformation of the glucocorticoid receptor (gr) into a fully activated transcription factor. however, the ability of camp to act synergistica ...19938383286
glucocorticoid-regulated stability of a constitutively expressed mouse mammary tumor virus glycoprotein.glucocorticoids regulate the transport and processing of mouse mammary tumor virus (mmtv) glycoproteins in viral-infected htc rat hepatoma cells. to begin to determine the role of cellular components involved in this steroid-mediated response, a constitutively expressed mmtv glycoprotein gene containing a mutation in the endoproteolytic cleavage site was used to simplify the viral maturation products. expression of the uncleavable mmtv glycoprotein gene in transfected htc rat hepatoma cells demo ...19938383289
characterization of mammary plaques in ddd mice congenic for mtv-2 gene, ddd/1-mtv-2/mtv-2.ddd/1 mice free from exogenous mouse mammary tumor virus (mmtv) do not develop any neoplastic mammary lesions. in gr mice, the expression of mtv-2, an endogenous proviral mmtv, leads to 100% incidence of mammary ductal hyperplasias and tumors. an mtv-2 congenic line, ddd/1-mtv-2/mtv-2, was established by introducing mtv-2 from gr into ddd/1 to elucidate its function. development of mammary plaques (mpq) characterized by ductal hyperplasias was investigated in 152 congenic females on day 17 to 19 ...19938383648
tissue distribution of mtv-7-like exogenous retroviral transcripts and clonal deletion of v beta 6+ t cells in mls-1b balb/c mice.we have previously described an mls-1a-like clonal deletion of mature cd4+ t cells which express v beta 6 and v beta 8.1 chains of the tcr in half of the mice of a balb/c, mls-1b colony (balb/c ic). this occurs in the absence of the mtv-7 provirus which is responsible for the clonal deletion in mls-1a mice. we developed a polymerase chain reaction assay in order to study the presence of retroviral transcripts homologous to the viral superantigen gene (vsag) of mtv-7 and mtv-6 in various tissues. ...19938383996
development of a recombinant bovine leukemia virus vector for delivery of a synthetic bovine growth hormone-releasing factor gene into bovine cells.continuous intravenous infusion of bovine growth hormone-releasing factor (bgrf) increases milk synthesis in dairy cattle by as much as 46%. we have begun to develop a system for delivery and expression of a synthetic bgrf gene in cultured bovine cells using the provirus of the bovine leukemia virus (blv). the gene encoding synthetic bgrf, constructed from eight overlapping oligonucleotides, was fused to the whey acidic protein promoter (wap) or the mouse mammary tumor virus promoter (mmtv). the ...19938385087
relationship between defective mouse mammary tumor virus envelope glycoprotein synthesis and grp78 synthesis in glucocorticoid-treated mouse lymphoma cells. evidence for translational control of grp78 synthesis.we have found that synthesis of the 78-kda glucose-regulated protein, grp78, was increased following glucocorticoid treatment of s49 and w7mg1 mouse lymphoma cell lines. these lines synthesized a 74-kda mouse mammary tumor virus envelope glycoprotein precursor, pr74, both constitutively and in response to glucocorticoid treatment. in these cell lines, nascent pr74 was not processed normally but was retained within the endoplasmic reticulum where it was bound stably by grp78. grp78 synthesis was ...19938385109
positive regulation of trna gene expression by the mouse mammary tumor virus-long terminal repeat in vitro.the mouse mammary tumor virus long terminal repeat (mmtv-ltr) participates in the control of gene expression by providing a series of important dna binding sites at which trans-acting factors interact. among these factors are the steroid receptor, nuclear factor i (nfi) and the tata box factor (tfiid). the binding of these proteins facilitates the assembly of a transcriptionally competent complex, that includes rna polymerase ii, and activates the expression of juxtaposed genes in cis. a particu ...19938385315
wild-type adenovirus type 5 transforming genes function as transdominant suppressors of oncogenesis in mutant adenovirus type 5 transformed rat embryo fibroblast cells.transformation of cloned rat embryo fibroblast (cref) cells with the host-range adenovirus type 5 (ad5) mutant, h5hr1, results in transformants with a fibroblastic morphology which displays a cold-sensitive transformation phenotype and oncogenic potential in both nude mice and syngeneic rats. in contrast, wild-type (wt) ad5 transformed cref cells are epithelioid in morphology, temperature independent for transformation, and nontumorigenic. the present studies were conducted to analyze the contri ...19938385576
characterization of experimental allergic encephalomyelitis-susceptible, biozzi ab/h (h-2dq1) mice which express h-2anod: analysis of t-cell receptor expression and the detection of a deletion ligand encoded by mtv-7.biozzi (h-2dq1) ab/h mice are marked not only by their high titre antibody responses following immunization with protein antigens but are also susceptible to experimental allergic encephalomyelitis (eae) induction. the t-cell receptor (tcr) repertoire in this recently characterized strain was analysed. biozzi ab/h mice were found to express the thy-1a, ly-1b, ly-2b and ly-5b alleles. serological typing of the tcr-v beta + peripheral t cells suggested that the ab/h mice belong to the tcr-v beta b ...19938386133
transient promoter activity in primary rat mammary epithelial cells evaluated using particle bombardment gene transfer.the relative strengths of several commonly used viral promoters in primary cultures of rat mammary epithelial cells were studied using a particle bombardment gene transfer method. nih 3t3 cells were also examined as a representative cell line. initially, the conditions necessary for efficient gene transfer using particle bombardment were determined. discharge voltage for particle bombardment was evaluated to maximize the levels of gene expression and cell viability. after transfection, transgene ...19938386156
peripheral t cell activation and deletion induced by transfer of lymphocyte subsets expressing endogenous or exogenous mouse mammary tumor virus.murine t cell reactivity with products of the minor lymphocyte stimulatory (mls) locus correlates with the expression of particular variable (v) domains of the t cell receptor (tcr) beta chain. it was recently demonstrated that mls antigens are encoded by an open reading frame (orf) in the 3' long terminal repeat of either endogenous or exogenous mouse mammary tumor virus (mmtv). immature thymocytes expressing reactive tcr-v beta domains are clonally deleted upon exposure to endogenous mtv's. ma ...19938386743
distinct amounts of polyomavirus large t antigen are required for different functions of the protein.many cellular and some virally coded proteins regulating key events in higher cells have been found to be multifunctional. one example of such a protein is the polyomavirus large t antigen, which is involved not only in viral dna replication and gene expression but also in the induction of the s phase in host cells, in the immortalization of various cell types and in the transactivation of some cellular genes. we recently constructed cell lines in which t antigen was synthesized under the contro ...19938386826
activation of both wnt-1 and fgf-3 by insertion of mouse mammary tumor virus downstream in the reverse orientation: a reappraisal of the enhancer insertion model.in retrovirus-induced tumors, proviral dna is commonly found next to or within a cellular proto-oncogene such that transcription of the gene is influenced by the viral promoter or enhancer. extensive surveys of naturally occurring tumors reveal that proviruses integrated on the 3' side of the gene are usually in the same transcriptional orientation, suggesting a model in which the bidirectional viral enhancer acts primarily on the closest promoters. here we describe a virally induced mammary tum ...19938386870
mls-1 superantigen: molecular characterization and functional analysis. 19938387454
influence of viral superantigens on v beta- and v alpha-specific positive and negative selection.in mice, v beta-specific negative selection is mediated by a number of superantigens encoded by various mouse mammary tumor viruses. we have identified mtv-3, mtv-27, mtv-44, mtv-8, mtv-9, mtv-11, and mmtv(d2.gd), and have confirmed mtv-1. although specificities of superantigens correlate well with sequences of their carboxy terminal regions, mtv-44 appears to be an exception: the product is specific for v beta 3, v beta 6, v beta 8.1, and v beta 9. it remains to be determined whether mtv-44 pro ...19938387455
exogenous and endogenous mouse mammary tumor virus superantigens. 19938387457
the bacterial and mouse mammary tumor virus superantigens; two different families of proteins with the same functions.in conclusion, the bacterial toxins are completely unlike the mtv superantigens in primary sequence and structure. the former are soluble globular proteins which do not have to be proteolytically cleaved before they act. the latter are synthesized as type ii membrane proteins and may be clipped before they reach the cell surface and act to stimulate t cells. table iii summarizes the similarities and differences between the two sets of superantigens. the most notable quality of these molecules is ...19938387458
t-cell receptor repertoire selection by mouse mammary tumor viruses and mhc molecules. 19938387459
t cell repertoire selection by mouse mammary tumour viruses.mouse mammary tumour viruses (mtv) are b-type retroviruses. these can be exogenous, transmitted via maternal milk, or endogenous, as proviral integrations into the mouse genome, transmitted vertically in a mendelian fashion. a number of different sites of integration of endogenous mtvs have been reported in various inbred mouse strains. an open reading frame (orf), within the long terminal repeat (ltr) of mtv, encodes a type 2 integral membrane glycoprotein. the orf products are expressed in ass ...19938388249
interaction of androgen and glucocorticoid receptor dna-binding domains with their response elements.fusion proteins containing the glucocorticoid and the androgen receptor dna-binding domain (arf1 and grf1) were produced in escherichia coli. dnase i footprinting was used to compare the interaction of these proteins with responsive elements (res) in a typically glucocorticoid-responsive gene (mouse mammary tumour virus (mmtv)) and in an androgen-responsive gene (the c3(1) gene of rat prostatic binding protein). it is demonstrated that response elements which most closely resemble the consensus ...19938388338
human t cells respond to mouse mammary tumor virus-encoded superantigen: v beta restriction and conserved evolutionary features.mouse mammary tumor virus (mmtv)-encoded superantigens (sags) influence the murine t cell repertoire and stimulate a strong mixed lymphocyte response in vitro. these sags are encoded by the open reading frame of the 3' long terminal repeat of mmtv, termed mmtv sags. the t cell response to mmtv sags is v beta restricted and requires expression of the class ii molecules of the major histocompatibility complex (mhc) on the presenting cells. while human t cells respond to bacterial sags, it is not k ...19938388432
the constitution of a progesterone response element.progesterone receptors (prs) recognize and bind to dna in a sequence-specific manner. to define the sequence-specific determinants of pr binding to dna, we employed a detailed series of target elements and analyzed both pr binding in vitro and pr-mediated activation of a reporter gene in vivo. these elements represent point substitution or insertion mutants of a progesterone response element derived from the mouse mammary tumor virus (mmtv). substitution of a g for the first t in the 15-base pai ...19938388996
cell-specific bifunctional role of jun oncogene family members on glucocorticoid receptor-dependent transcription.interaction between protein kinase c (pkc)- and glucocorticoid receptor (gr)-mediated signaling is suggested by the ability of the pkc activating phorbol ester 12-o-tetradecanoylphorbol-13-acetate (tpa) to inhibit gr-dependent transcription of the mouse mammary tumor virus (mmtv) long terminal repeat (ltr). here we report that this interference is cell specific, as tpa augmented dexamethasone-induced transcriptional activation of the mmtv ltr in several t cell lines but was inhibitory in nih-3t3 ...19938388998
characterization of the interaction of the human mineralocorticosteroid receptor with hormone response elements.although the mineralocorticosteroid receptor (mr) belongs to the superfamily of hormone-dependent transcription factors, the molecular mechanism by which it regulates gene expression is poorly understood. binding of the mr to target gene promoters has never been characterized, and specific mineralocorticosteroid response elements (mres) remain to be identified. the human mr (hmr) was overexpressed in sf21 insect cells using the baculovirus system. the high degree of similarity between the glucoc ...19938389140
histones, nucleosomes and transcription.it is becoming increasingly clear that nucleosome structure is integrally involved in gene regulation. in particular, the study of inducible genes has shown that nucleosomes not only contribute to a repressed basal state, but can also be rearranged in response to induction. the mechanism of this process is just beginning to be elucidated, and genetic studies have implicated several proteins in the modulation of nucleosome structure.19938389216
a new strain congenic for the mtv-7/mls-1 locus of mouse chromosome 1. 19938389322
the progesterone antagonist ru486 acquires agonist activity upon stimulation of camp signaling pathways.the protein kinase a stimulator camp can potentiate the ability of progestins to induce the transactivation function of the human progesterone receptor (hpr). we questioned in the present study whether camp could functionally cooperate with the progestin antagonist ru486. in t47d human breast cancer cells, ru486 behaves as a pure antagonist with respect to induction of the progesterone-responsive mouse mammary tumor virus chloramphenicol acetyltransferase (mmtv-cat) reporter gene. it fails to st ...19938389450
the cytoplasmic raf oncogene induces a neuronal phenotype in pc12 cells: a potential role for cellular raf kinases in neuronal growth factor signal transduction.the neuron-like differentiation of pc12 cells is induced by nerve growth factor (ngf) through stimulation of a membrane-bound protooncoprotein signaling pathway containing the ngf receptor trk, the tyrosine kinase src, and the gtp-binding protein ras. the raf-1 and b-raf protooncogenes encode cytoplasmic serine/threonine kinases that are stimulated by ngf in a ras-dependent manner. to investigate the possible roles of cytoplasmic raf kinases in eliciting neuronal differentiation, we have express ...19938389463
linkage of superantigen-like stimulation of syngeneic t cells in a mouse model of follicular center b cell lymphoma to transcription of endogenous mammary tumor virus.the mhc class ii i-a(s) positive b cell lymphomas reticulum cell sarcoma (rcs) that arise in > 90% of sjl mice by the age of 12 months have superantigen-like stimulating properties. in the present study, therefore, rcs cell lines were examined for abnormal expression of endogenous mouse mammary tumor virus (mmtv) proviruses. extraordinarily high expression of a 1.8 kb mrna hybridizing with the long terminal repeat (ltr) of mmtv was found in both primary lymphomas and in vitro rcs lines, but not ...19938389694
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