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molecular insights into breast cancer from transgenic mouse models.we desperately need to know more of the biological details of the onset and progression of breast cancer. the disease is of startlingly high incidence (approaching 1 in 9 women), our current therapies for the disease are inadequate once it has metastasized, and the disease is characterized by excessive morbidity and mortality. most of the growth and differentiation of the mammary gland occurs relatively late in life: during sexual maturation, and then cyclically during pregnancy and lactation. n ...19911663341
rna pseudoknots downstream of the frameshift sites of retroviruses.rna pseudoknot structural motifs could have implications for a wide range of biological processes of rnas. in this study, the potential rna pseudoknots just downstream from the known and suspected retroviral frame-shift sites were predicted in the rous sarcoma virus, primate immunodeficiency viruses (hiv-1, hiv-2, and siv), equine infectious anemia virus, visna virus, bovine leukemia virus, human t-cell leukemia virus (types i and ii), mouse mammary tumor virus, mason-pfizer monkey virus, and si ...19911663382
tissue distribution of the cellular binding protein for the mouse mammary tumour virus.the envelope protein, gp52, of the mouse mammary tumour virus (mmtv) binds to a cell-surface receptor as a first step in infection. a protein with characteristics of this receptor was measured on freshly isolated cells using, as ligand, 125i-labelled gp52 purified from c3h/hen mice. the gp52-binding protein was found in all mouse tissues examined, but was present at highest concentrations in the mammary gland and spleen where it reached 4.2 +/- 0.3 (s.e.m.) pmol/mg protein; the dissociation cons ...19911663754
tissue distribution of mouse mammary tumor virus (mmtv) antigens and new endogenous mmtv loci in japanese laboratory mouse strains.the distribution of mouse mammary tumor virus (mmtv) antigens was studied by the immunoperoxidase method in the ii-tes and i-tes mouse strains as well as their progenitors, cs and dba/2 strains. in the ii-tes, i-tes and cs strains, and balb/c mice foster-nursed with these strains, mmtv antigens were found not only in epithelial cells of the mammary glands but also in those of other tissues including the seminal vesicle, vas deferens, epididymis, prostate, parotid, submandibular, lacrimal, sebace ...19911663921
altered effects of glucocorticoids on the trafficking and processing of mouse mammary tumor virus glycoproteins constitutively expressed in rat hepatoma cells in the absence of nonglycosylated viral components.we have documented previously that glucocorticoid hormones modulate the posttranslational localization of cell surface mouse mammary tumor virus (mmtv) glycoproteins in the viral-infected m1.54 rat htc hepatoma cell line. to determine whether glucocorticoids affect the trafficking of individually synthesized mmtv glycoproteins, htc cells were transfected with a constitutively expressed mmtv glycoprotein gene lacking the viral phosphoprotein and polymerase genes. this construct also allows equiva ...19911664047
sequence homology of deoxyribonucleic acid to mouse mammary tumor virus genome in human breast tumors.fifty-two human breast tumors were screened for the presence of dna homology to mouse mammary tumor virus (mmtv) using molecularly cloned mmtv proviral genomic dna probes and dot-blot hybridization. seven patients were found to contain an entire provirus (gag, pol, env, and ltr positive at high stringency). fifty percent (5/10) of patients having a first degree relative with breast carcinoma were found to have dna homology to the gag-pol portion of the mmtv genome when hybridization and washing ...19911664195
regulation of the mouse mammary tumor virus (mmtv) binding site in cultured mammary tissue.the mouse mammary tumor virus (mmtv) initiates infection when the envelope protein, gp52, binds to a cell surface protein and triggers internalization. the hormonal regulation of this protein was studied both in vitro and in vivo. in mammary gland explant culture, levels of the mmtv binding protein were maintained only when prolactin was present in the medium. the further addition of progesterone induced levels to 164% of controls, while estradiol was without effect. these results were reproduce ...19911665450
in two genes, synergism of steroid hormone action is not mediated by cooperative binding of receptors to adjacent sites.synergistic action of multiple steroid hormone response elements (hres) has been proposed to be due to cooperative binding of receptors. we have studied the cooperativity of steroid hormone receptor binding to synergistic hres in two natural genes. in the mouse mammary tumor virus long terminal repeat that contains four progesterone receptor binding sites, no cooperativity in receptor binding was observed between the single distal and the three proximal sites whereas a low level of cooperativity ...19911665457
binding of glucocorticoid receptors to model dna response elements.dna sequences were synthesized that contained the consensus 15-base pair glucocorticoid receptor binding site linked to flanking sequences of various lengths. binding of these synthetic oligomers to glucocorticoid receptor, employing a reconstituted binding system with purified components, indicated that a minimal size of approximately 45 base pairs was necessary to bind the receptor optimally. sequences containing multiple receptor binding sites competed more effectively for binding. these find ...19911665494
establishment and characterization of immortalized non-transplantable mouse mammary cell lines cloned from a mmtv-induced tumor cell line cultured for a long duration.during the culturing of a mouse mammary tumor cell line, mumt73, maintained in vitro for more than a decade, we found morphological heterogeneity in its cells; some showed contact inhibition in their growth, some formed domes and some grew criss cross and piled up. in trying to clone the cell line to isolate cells showing contact inhibition or dome formation, we were able to establish six clonal cell lines. these six cell lines were categorically divided into three groups according to their phen ...19911666666
oncogenes and breast cancer progression. 19911667570
identification and characterization of differentially expressed genes in tumor metastasis: the nm23 gene. 19911667573
insertional mutagenesis in mouse mammary tumorigenesis. 19911667629
in vitro cleavage of an n-ras messenger-like rna by a ribozyme.a cdna library was constructed in lambda gt10 from t-15 cells, a transformed mouse fibroblast line. the transforming n-ras sequence was recovered and subsequently used as a substrate for ribozyme cleavage. the design of the ribozyme was based on that of the hammerhead structure of the satellite tobacco ringspot autolytic processing sequence. specificity to the n-ras substrate was conferred by 10 nucleotides homologous to the target site on the mrna positioned on either side of the catalytic unit ...19911668256
generation of c127-derived cell lines expressing estrogen or progesterone receptors for studying gene regulation on bovine papilloma virus minichromosomes.to study regulation of transcription by multiple steroid hormones we have stably introduced expression vectors for human estrogen and rabbit progesterone receptors into the genome of the murine fibroblast cell line c127. these cells express functional endogenous glucocorticoid receptor and support bovine papilloma virus minichromosomes, a useful system for studying the role of chromatin structure on gene expression. three clones containing progesterone receptor integrates and six containing estr ...19911668831
expression and function of normal and lncap androgen receptors in androgen-insensitive human prostatic cancer cells. altered hormone and antihormone specificity in gene transactivation.the gene for the androgen receptor (ar) in the androgen-sensitive human prostate cancer cell line lncap has a single-base mutation that produces a threonine to alanine change in the androgen-binding domain. androgen-insensitive prostatic cancer (pc-3) cells were cotransfected with an expression vector encoding normal, lncap, or chimeric normal/lncap ar and a vector carrying a chloramphenicol acetyltransferase (cat) reporter gene linked to the mouse mammary tumor virus promoter. cat activity was ...19911668832
transgenic models of human cancer.transgenic animal technology has been useful for the direct demonstration of the tumorigenic potential of oncogenes in vivo. over the past eight years a wide variety of oncogenes and proto-oncogenes from viral and cellular sources have been inserted into the germline of mice with subsequent development of neoplasia. many of the published reports describe similarities between morphologic features of the transgenic mice tumors and those occurring naturally in humans. we discuss the morphologic fea ...19911668887
identification and applications of repetitive probes for gene mapping in the mouse.interspecific mouse hybrids that are viable and fertile provide a wealth of genetic variation that is useful for gene mapping. we are using this genetic variation to develop multilocus linkage maps of the mouse genome. as an outgrowth of this work, we have identified three repetitive probes that collectively identify 28 loci dispersed on 16 of the 19 mouse autosomes and the x chromosome. these loci establish a skeleton linkage map that can be used to detect linkage over much of the mouse genome. ...19911673105
on the importance of taking a firm position. chromatin structure and gene expression sponsored by fundación juan march, madrid, spain september 24-26, 1990. 19911674885
evidence for quantitative and qualitative differences in functional activation of mls-reactive t cell clones and hybridomas by antigen or tcr/cd3 antibodies.in this study, we demonstrated that some v beta 6+, cd4+, mls-1a-specific t cell clones had cytolytic activity when stimulated with anti-t cell receptor(tcr)/cd3 monoclonal antibodies (mab), but not with targets expressing mls-1a, although they produced lymphokines (interleukin 2 and interferon-gamma) in response to both types of stimuli. to examine the possibility that lack of cytolysis resulted from expression of the mls-1a antigen on merely a fraction of splenic b blasts, we (a) used the b ce ...19911680703
chromatin structure of hormono-dependent promoters.transient transfections of mutated mmtv ltrs, driving the luciferase reporter gene, have shown the presence of at least one cis-acting element cooperating with the gres. studies of the chromatin structure of two glucocorticoid-regulated promoters, the mouse mammary tumor virus (mmtv) long terminal repeat (ltr), a retroviral promoter, and the rat tyrosine aminotransferase (tat) promoter, demonstrate that both dnas are organized into precisely positioned nucleosomes. hormonal activation of transcr ...19911683563
the mechanism for glucocorticoid-resistance in a rat hepatoma cell variant that contains functional glucocorticoid receptor.the mechanism of glucocorticoid resistance has been studied in a rat hepatoma cell variant (6.10.2), which contains low levels of glucocorticoid receptor (gr). these cells seem to have lost all the glucocorticoid-induced transcriptional responses as measured by the lack of induction of expression of stably integrated mouse mammary tumor virus (mmtv) and the endogenous gene tyrosine aminotransferase (tat), as well as the transcriptional suppression of gr gene expression. physico-chemical characte ...19911683564
the int-2 gene product acts as an epithelial growth factor in transgenic mice.the induction of mammary tumors by mouse mammary tumor virus (mmtv) is thought to occur through proviral activation of one or more cellular genes. one of these, int-2, encodes a 27 kd protein which exhibits striking homology to the basic fibroblast growth factor family. to assess directly the role of the int-2 protein in cell proliferation, we have established transgenic mice which carry the int-2 gene driven by the mmtv promoter/enhancer. expression of the int-2 gene in female transgenic mice r ...19901690126
lack of evidence for the involvement of type-c and type-b retroviruses in radiation leukemogenesis of nfs mice.southern blot analysis revealed no difference between the dna from radiation-induced thymic lymphomas and dna from normal nfs mice. the probes used in the southern blot analyses used a murine leukemia virus (mulv) env dna probe (pxenv), which specifically hybridizes with xenotropic and recombinant viral env genes, and mouse mammary tumor virus (mmtv) dna probes (mmtv gag-pol, mmtv env, and mmtv ltr). this suggests that radiation leukemogenesis was not associated with gross alteration of the orga ...19901690435
oncogenicity of the ret transforming gene in mmtv/ret transgenic mice.we have successfully produced transgenic mice that carry the ret oncogene driven by a mouse mammary tumor virus promoter/enhancer. mammary and salivary gland adenocarcinomas were developed in a stochastic fashion in these mice. moreover, premalignant tumors with hyperplastic and dysplastic lesions of harderian glands and male reproductive tracts frequently occurred at young ages. high expression of the transgene was closely associated with the development of these tumors although the levels of t ...19901691479
the wnt-1 (int-1) oncogene promoter and its mechanism of activation by insertion of proviral dna of the mouse mammary tumor virus.wnt-1 (int-1) is a cellular oncogene often activated by insertion of proviral dna of the mouse mammary tumor virus. we have mapped the 5' end and the promoter area of the wnt-1 gene by nuclease protection and primer extension assays. in differentiating p19 embryonal carcinoma cells, in which wnt-1 is naturally expressed, two start sites of transcription were found, one preceded by two tata boxes and one preceded by several gc boxes. in p19 cells, a 1-kilobase upstream sequence of wnt-1 was able ...19901695322
regulated expression of vimentin cdna in cells in the presence and absence of a preexisting vimentin filament network.human cells were transfected with a mouse vimentin cdna expression vector containing the hormone response element of mouse mammary tumor virus. the distribution of mouse vimentin after induction with dexamethasone was examined by indirect immunofluorescence with antivimentin antibodies specific for either mouse or human vimentin. in stably transfected hela cells, which contain vimentin filaments, addition of dexamethasone resulted in the initial appearance of mouse vimentin in discrete areas, us ...19901696263
altered mouse mammary tumor virus transcript synthesis in t-cell lymphoma cells.proviral copies of mouse mammary tumor virus (mmtv) are known to be amplified in certain t-cell lymphomas. transcription of the amplified mmtv proviruses was studied in detail in two t-cell lymphoma lines and showed the production of deletions and premature termination of env mrnas and the premature termination of gag transcripts. el-4 cells produce three env mrnas, and sequence analysis of cdnas of the two smaller transcripts revealed large deletions encompassing the 3' half of the env gene. th ...19901696633
immortalization and transformation of human fibroblasts by regulated expression of polyoma virus t antigens.we have established conditions for the immortalization of human fibroblasts by the large t antigen of the rodent virus polyoma. this allows the mechanism of immortalization to be studied, without interference by transformation events, in cells with relatively stable chromosomes. large t antigen could immortalize human fibroblasts if expression was driven by a heterologous promoter like the immediate early promoter/enhancer of cytomegalovirus or the inducible mouse mammary tumour virus (mmtv) pro ...19901697410
gene expression in cells infected with gammaherpesvirus saimiri: properties of transcripts from two immediate-early genes.during productive infections of cells with the gammaherpesvirus, herpesvirus saimiri (hvs), a polyadenylated rna of 2.2-2.4 kb accumulates to form a large fraction of virus-specified rna. this transcript is from the virus thymidylate synthase (ts) gene and its synthesis, like that of late mrnas encoding the virus structural proteins, is sensitive to an inhibitor of virus dna synthesis (phosphonoacetic acid, paa). transcription which is insensitive to paa occurs from many parts of the hvs genome, ...19901699352
negative regulation in correct tissue-specific expression of mouse mammary tumor virus in transgenic mice.mouse mammary tumor virus (mmtv) is an endogenous murine retrovirus that is expressed in the epithelial cells of the mammary and salivary glands, lungs, kidneys, and seminal vesicles and in the lymphoid cells of the spleen and thymus. several studies have shown that the long terminal repeat (ltr) of this virus can direct the expression of reporter genes to the same tissues in transgenic mice. to determine whether multiple regulatory elements within the ltr are involved in this tissue-specific ex ...19901700274
characterization of int-5, a locus associated with early events in mammary carcinogenesis.three chemically-induced precancerous mammary hyperplasias, independently isolated in balb/c mice, all contained mouse mammary tumor virus (mmtv) proviral dna integrated into a common region in chromosomal dna, designated int-5 (formerly int-h, gray et al., 1986). this site was cloned from a hyperplastic outgrowth (d2) into lambda phage. a 1.7 kb hind iii dna fragment, which flanks the 5' end of the mmtv insert, was generated from the cloned int-5 region. this fragment was used as probe (ih-2) t ...19911705320
a superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus.mice express a collection of superantigens, which bind to class ii major histocompatibility proteins and interact with t cells bearing particular v beta chains as part of their alpha beta receptors. these superantigens have been suggested to be encoded by exogenous or endogenous mouse mammary tumour viruses. one such superantigen is now shown to be encoded in the open reading frame of the long terminal repeat of a mammary tumour virus, a gene of previously unknown function.19911706480
two regions of the mouse mammary tumor virus long terminal repeat regulate the activity of its promoter in mammary cell lines.in vivo expression of the mouse mammary tumor virus (mmtv) is restricted to a few organs, with the highest rate of transcription found in the mammary gland. using a series of mammary and nonmammary murine cell lines, we have identified two regulatory elements, located upstream of the hormone responsive element, that specifically regulate the mmtv promoter. the first element displays an enhancerlike activity and is coincident with the binding of a nuclear factor (designated mp4; position -1078 to ...19911708094
a new approach combining interferon and bromocriptine la to prevent spontaneous mouse mammary carcinoma.the development of spontaneous mammary carcinoma in c3h mice is mainly attributed to an oncogenic virus (mmtv) and the high prolactin levels of this inbred strain. interferon (ifn) reduces the incidence of mammary carcinoma in virgin c3h mice when administered during lactation. bromocriptine la, an antiprolactin drug, also decreases the incidence of this tumor in c3h mice. the combined action of mouse ifn-alpha + beta and bromocriptine la had a significant anticarcinogenic effect more significan ...19911709419
a novel bk virus-based episomal vector for expression of foreign genes in mammalian cells.a composite mammalian cell-e. coli shuttle vector was developed based on the human papova virus bk and psv-neo. the vector contains a dioxin-responsive enhancer (dre) controlling a mouse mammary tumor virus (mmtv) promoter for the inducible expression of inserted genes. in human cells the vector replicates episomally, presumably utilizing the bkv rather than the sv40 origin, and expresses the bk t/t antigens. a deletion in the late bk region precludes the expression of the core/capsid proteins v ...19911709496
molecular biology of type a endogenous retrovirus.intracisternal a particles (iaps) are retrovirus-like structures consistently observable in a variety of mouse tumor cells such as myeloma and hybridoma and in early embryonic cells derived from rodents but nothing is known of their infectivity. mouse iaps contain a gag-like protein, a reverse transcriptase and a polyadenylated rna molecule (iap rna). dna sequences complementary to iap rna (iap genome) are interspersedly present in rodent such as mice, rats, chinese hamsters and syrian hamsters ...19901710682
suppression of adenovirus type 5 e1a-mediated transformation and expression of the transformed phenotype by caffeic acid phenethyl ester (cape).viral transformation and dna-transfection assays were employed to investigate the differential toxic effect of caffeic acid phenethyl ester (cape), an extract of the honeybee hive product propolis, on adenovirus type 5 (ad5)-transformed cloned rat embryo fibroblast (cref) cells. cape inhibited, in a dose-dependent manner, both de novo and carcinogen-enhanced transformation of cref cells by h5hr1, the cold-sensitive (cs) host-range mutant of ad5. cape had a selective inhibitory effect on ad5-indu ...19911712205
host genetic background effect on the frequency of mouse mammary tumor virus-induced rearrangements of the int-1 and int-2 loci in mouse mammary tumors.the frequency with which int-1 and int-2 are rearranged in mouse mammary tumors by mouse mammary tumor virus (mmtv)-induced insertional mutagenesis is a consequence of the host genetic background. in 75% of c3h mammary tumors, int-1 is rearranged by mmtv insertion, whereas only 30% of balb/cfc3h tumors contain a virus-induced rearrangement of int-1. this difference is significant (p less than 0.005) and could not be accounted for by the potentially additive effect of the genetically transmitted ...19911712864
glucocorticoid induction of the adipocyte clone 5 gene requires high cell density.we have previously reported the identification of a glucocorticoid and cell-density inducible gene (clone 5) that appears to play a regulatory role in adipocyte differentiation. in the current studies we have more carefully investigated the interplay between cell growth or differentiation and the glucocorticoid responsiveness of clone 5 rna. we find that inducibility by steroid hormone is independent of the differentiated state but surprisingly, occurs only when cells are at high cell density. i ...19911712909
myoepitheliomas in inbred laboratory mice.myoepitheliomas are subcutaneous tumors that arise from myoepithelial cells of various exocrine glands. in a retrospective study of 142 tumors observed over a period of 3 years, myoepitheliomas occurred spontaneously in a/hej, a/j, balb/cj, balb/cbyj, llc.a/ckc, and nod/lt inbred strains of mice. tumors presented primarily in the subcutaneous tissues of the ventral neck (74% of the myoepitheliomas evaluated) but were observed in several other subcutaneous locations, including the head, perineum, ...19911719689
ras oncogenes amplify lymphokine (interleukin 3, granulocyte-macrophage colony-stimulating factor) induction by calcium ionophore.interleukin 3 (il-3) expression in pb-3c mastocytes is transiently induced in vitro by treatment with the drug a23187, a calcium ionophore, or constitutively following ras-dependent transformation in vivo. while the mechanism of oncogenically induced il-3 expression is not clear, a23187-mediated lymphokine mrna accumulation is primarily the result of calcium-dependent mrna stabilization. we investigated whether the expression of various ras alleles influenced il-3 and granulocyte-macrophage colo ...19911722572
tightly bound zinc in human immunodeficiency virus type 1, human t-cell leukemia virus type i, and other retroviruses.human immunodeficiency virus type 1 (hiv-1) and human t-cell leukemia virus type i (htlv-i) were purified by sucrose density gradient centrifugation in the presence of 1 mm edta. pelleted gradient fractions were analyzed for total protein, total gag capsid protein, and total zinc. zinc was found to copurify and concentrate with the virus particles. through successive cycles of resuspending in buffer containing edta and repelleting, the zinc content remained constant at about 1.7 mol of zinc per ...19921731111
[on the mechanisms of retardation of aging and inhibition of mammary tumorigenesis by energy restriction in shn/c3h f1 female mice].although it has long been known that energy restriction (er) inhibits tumors and retards aging in rats and mice, its mode of action remains unknown. in rodents, er alters the rate of age-related changes in physiological indices. thus, it affects a broad array of age-sensitive parameters. however, present evidence does not indicate which parameters are primary contributors to the deceleration of aging. compared to fasting or short-term underfeeding, little is known about the metabolic effects of ...19911749105
mixed inocula of mouse mammary tumour cell subpopulations result in changes of organ-specific metastasis.tumour and metastatic phenotypes, the pattern of mouse mammary tumour virus (mmtv) integration and expression, and the expression of a metastasis associated gene, nm23, were examined in three mammary tumour cell subpopulations, 66, 168 and 4526. tumour growth, host survival, metastatic aggressiveness, and the distribution of different cell types in metastasis resulting from mixed cell inocula were also analysed. the results of these studies indicated that the cell lines were distinguishable from ...19911752081
a heterologous hormone response element enhances expression of rat beta-casein promoter-driven chloramphenicol acetyltransferase fusion genes in the mammary gland of transgenic mice.previous studies have demonstrated that the entire rat beta-casein (r beta c) gene and a -524/+490 r beta c fragment-chloramphenicol acetyltransferase (cat) fusion gene are expressed preferentially in the mammary gland of transgenic mice in a developmentally regulated fashion. however, transgene expression was infrequent, less than 1% of that observed for the endogenous gene, and varied as much as 500-fold, presumably due to the site of chromosomal integration. to determine whether a heterologou ...19911775134
expression of a human monoclonal anti-hiv-1 antibody in cho cells.the cdna coding for the light and heavy chains, respectively, of the human monoclonal antibody 3d6 (igg1, kappa), which binds specifically to human immunodeficiency virus-1 (hiv-1) gp41, was inserted into three different mammalian expression vectors and transfected into chinese hamster ovary (cho) cells. transcription was under the control of rous sarcoma virus long terminal repeat (rsv ltr), human cytomegalovirus major immediate early (cmv ie) promoter, and mouse mammary tumor virus long termin ...19911809191
transcriptional activation by tr3 receptor, a member of the steroid receptor superfamily.tr3 receptor is a human homolog of mouse nurr77 and n10 protein and the rat ngfi-b protein. a cdna encoding a chimeric nuclear receptor composed of the n-terminal domain and c-terminal putative ligand-binding domain of the orphan receptor tr3 receptor and the dna-binding domain of the androgen receptor was constructed. the chimeric receptor, called tr3/ar/tr3 receptor, when expressed in cos-1 monkey kidney cells or pc-3 human prostate tumor cells, cotransfected with an are-containing mouse mamma ...19911843211
determinants of retrovirus gene expression in embryonal carcinoma cells.the expression of moloney murine leukemia virus is restricted in embryonal carcinoma (ec) cells. to characterize specific mutations necessary for expression of retroviruses in ec cells, we analyzed the expression of retrovirus mutants and recombinants thereof in ec cell lines f9 and pcc4. dna sequence comparison and functional studies allowed us to define three point mutations in the enhancer region of the viral mutants at positions -345, -326, and -166 and two point mutations within the 5'-untr ...19911845898
identification of a novel mammary cell line-specific enhancer element in the long terminal repeat of mouse mammary tumor virus, which interacts with its hormone-responsive element.we analyzed the long terminal repeat (ltr) of mouse mammary tumor virus for sequences that influence its promoter activity by using the chloramphenicol acetyltransferase assay. a series of ltr deletion mutants and recombinants between ltr and simian virus 40 regulatory sequences were used for these studies. through transfection experiments in three different human cell lines (t47d, mcf-7, and hela), we identified a novel mammary cell line-specific enhancer element on a 98-bp banii fragment (from ...19911845907
a new nomenclature for int-1 and related genes: the wnt gene family. 19911846319
transcription factor access is mediated by accurately positioned nucleosomes on the mouse mammary tumor virus promoter.a fragment of the mouse mammary tumor virus (mmtv) promoter was reconstituted from pure histones into a dinucleosome with uniquely positioned octamer cores. core boundaries for the in vitro-assembled dinucleosome corresponded to the observed in vivo phasing pattern for long terminal repeat nucleosomes a and b. nuclear factor 1 (nf1), a constituent of the mmtv transcription initiation complex, was excluded from the assembled dinucleosome, whereas the glucocorticoid receptor was able to bind. duri ...19911846670
alpha b crystallin accumulation is a specific response to ha-ras and v-mos oncogene expression in mouse nih 3t3 fibroblasts.the conditional expression of the v-mos and ha-ras(ej) oncogenes in nih 3t3 cells leads to the accumulation of a 23-kda protein (p23) (r. klemenz, s. hoffmann, r. jaggi, and a.-k. werenskiold, oncogene 4:799-803, 1989). we purified p23 to homogeneity and determined part of the amino acid sequence. the obtained sequence is identical with that of the eye lens protein alpha b crystallin. northern (rna) blot and western immunoblot experiments were performed to demonstrate that alpha b crystallin mrn ...19911846673
ubiquitous transcription factor otf-1 mediates induction of the mmtv promoter through synergistic interaction with hormone receptors.steroid hormones induce transcription from the mouse mammary tumor virus (mmtv) promoter by complex mechanisms requiring binding of the hormone receptors to the hormone responsive element (hre) of the long terminal repeat region. here we show that the mmtv promoter contains two degenerated octamer motifs immediately upstream of the tata box that together bind otf-1 (oct-1, nfiii) with an affinity similar to the octamer consensus. in transfection experiments, mutation of these octamer motifs inte ...19911846780
a maternally inherited superantigen encoded by a mammary tumour virus.a collection of superantigens, molecules which in combination with class ii major histocompatibility complex (mhc) engage t cells bearing particular v beta chains as part of their alpha beta receptors, have recently been described. the mouse self superantigen, mls-1a, for example, in conjunction with many mhc class ii proteins, engages mouse t cells bearing v beta 6, 7, 8.1 and 9, almost regardless of the sequences of the other variable components of the receptors on the t cells. two types of su ...19911846947
linkage of mls genes to endogenous mammary tumour viruses of inbred mice.t cells that recognize self antigen are clonally deleted in the thymus--a maturation process that occurs in the context of histocompatibility molecules and the t-cell receptor. the minor lymphocyte stimulation antigens (mls) effect these deletions through interactions with the v beta portion of the t-cell receptor, thus mimicking bacterial 'superantigens'. intrigued by the fact that each known mls gene maps to the same chromosomal region as an endogenous mouse mammary tumour virus (mtv), we reev ...19911846948
an endogenous retrovirus mediating deletion of alpha beta t cells?a special class of self-antigens (endogenous superantigens) is capable of deleting many murine t cells on the basis of their expression of particular t-cell receptor v beta gene segments. in mice that endogenously express these antigens, tolerance is mediated in part by the clonal deletion of the relevant v beta-bearing t cells. the deletion of i-e-reactive v beta 5.2-bearing t cells is dependent on the coexpression of an i-e tolerogenic coligand (etc)14 and the gene for one of these coligands, ...19911846949
genes encoding ligands for deletion of v beta 11 t cells cosegregate with mammary tumour virus genomes.the t-cell receptor (tcr) repertoire is selected in the thymus after rearrangement of genes encoding tcr alpha and beta chains. selection is based on the recognition by newly emergent t cells of self-ligands associated with molecules of the major histocompatibility complex: some combinations result in positive selection, others in negative selection. negative selection, or clonal deletion, is an important mechanism for eliminating autoreactive t cells. a group of self-ligands involved in clonal ...19911846950
binary system for regulating transgene expression in mice: targeting int-2 gene expression with yeast gal4/uas control elements.we have developed a binary transgenic system that activates an otherwise silent transgene in the progeny of a simple genetic cross. the system consists of two types of transgenic mouse strains, targets and transactivators. a target strain bears a transgene controlled by yeast regulatory sequences (uas) that respond only to the yeast transcriptional activator gal4. a transactivator strain expresses an active gal4 gene that can be driven by any selected promoter. the current paradigm uses the muri ...19911846961
expression of endogenous mtv provirus transcripts in balb/c splenic lymphocytes.the presence of antigen(s) related to the exogenous milk-transmitted murine mammary tumor virus on the surface of balb/c splenic lymphocytes has been documented previously. since the balb/c strain lacks murine mammary tumor virus, the presence of murine mammary tumor virus-related antigen(s) on lymphocytes has been ascribed to expression of germinally transmitted mtv transcripts and proviruses were characterized to evaluate this hypothesis. transcripts from genomic size mtv provirus(es) accumula ...19911847745
mos-induced inhibition of glucocorticoid receptor function is mediated by fos.activation of glucocorticoid hormone-dependent transcription involves the binding of the glucocorticoid hormone to its receptor followed by a specific interaction of the hormone/receptor complex with glucocorticoid responsive elements in the promoter region of hormone-inducible genes. in stably transfected nih3t3 cells expressing the oncogene product of v-mos or fos, the expression from two glucocorticoid responsive promoters, mmtv ltr and metallothionein iia (mtiia), was shown to be impaired an ...19911847998
localization and induced expression of fusion genes in the rat lung.liposome-mediated gene transfer is useful for dna transfection into cells in culture. we wondered whether this method could be used to introduce new dna into the intact lung. fusion genes containing either the rous sarcoma virus (rsv) promoter or the mouse mammary tumor virus (mmtv) promoter (which contains glucocorticoid response elements) were linked to the bacterial gene chloramphenicol acetyltransferase (cat), an enzyme not present in mammalian cells. plasmids containing the rsv-cat fusion g ...19911848084
clonal deletion of v beta 14-bearing t cells in mice transgenic for mammary tumour virus.autoreactive t lymphocytes are clonally deleted during maturation in the thymus. deletion of t cells expressing particular receptor v beta elements is controlled by poorly defined autosomal dominant genes. a gene has now been identified by expression of transgenes in mice which causes deletion of v beta 14+ t cells. the gene lies in the open reading frame of the long terminal repeat of the mouse mammary tumour virus.19911848685
incomplete proviral genome of mouse mammary tumour virus is present on chromosome y of nih swiss and some genetically related mouse strains.an incomplete proviral genome of endogenous mammary tumour virus (mmtv) was found in dna of several strains of mice. this mmtv-related sequence was assigned to the y chromosome since it was clearly observed in male mice only. this mmtv provirus contained a sequence related to ltr (long terminal repeat), but not to gag-pol and env genes. nfs, nih swiss/s, sts/a, and dd/tbr mice have this sequence but balb/chea, shn, sln, c57bl/6njcl, c3h/henjcl and cba/jjcl mice are negative. in the strains conta ...19911849209
histone hyperacetylation does not alter the positioning or stability of phased nucleosomes on the mouse mammary tumor virus long terminal repeat.activation of mouse mammary tumor virus transcription by the hormone-bound glucocorticoid receptor results in disruption of a nucleosome that is specifically positioned on the promoter. limited treatment of cells with the histone deacetylase inhibitor sodium butyrate prevents receptor-dependent promoter activation and nucleosome disruption [bresnick, e. h., john, s., berard, d. s., lefebvre, p., & hager, g. l. (1990) proc. natl. acad. sci. u.s.a. 87, 3977-3981]. on the basis of this observation, ...19911849427
cooperation between structural elements in hormono-regulated transcription from the mouse mammary tumor virus promoter.the mouse mammary tumor virus (mmtv) promoter is under the control of several types of regulatory agents. the proximal promoter within the long terminal repeat (ltr), from -200 to the cap site and its regulation by steroid hormones have been extensively studied. however the precise role of sequences located upstream of this region remain unclear. we have constructed mmtv ltr deletion mutants coupled to the luciferase reporter gene and assayed their activities after transient transfection into tr ...19911851294
androgen resistance associated with a mutation of the androgen receptor at amino acid 772 (arg----cys) results from a combination of decreased messenger ribonucleic acid levels and impairment of receptor function.analysis of the nucleotide sequence of the coding segment of the androgen receptor gene in a patient (n105) with the receptor-negative form of complete testicular feminization has revealed a single substitution (cgc----tgc) at nucleotide 2476. this alteration results in the conversion of an arginine at amino acid 772 to a cysteine. introduction of this mutation into an androgen receptor cdna and transfection of the mutant cdna into cos cells result in the production of a receptor protein with an ...19911856263
neither the endogenous nor a functional steroid hormone receptor binding site transactivate the ribosomal rna gene promoter in vitro.the mammalian ribosomal rna gene promoters exhibit a conserved sequence between positions +1 and +16 that shows a high degree of homology to the response element for glucocorticoids and progestins (gre/pre). these sequences bind specifically the glucocorticoid receptor and the progesterone receptor (pr) albeit with lower affinity than a canonical gre/pre. because steroid hormones are known to affect expression of the ribosomal genes, we tested the influence of hormone receptors on the activity o ...19911911432
glucocorticoid growth suppression response in 13762nf adenocarcinoma-derived con8 rat mammary tumor cells is mediated by dominant trans-acting factors.the in vitro and in vivo growth of con8 cells, a single cell-derived subclone of the 13762nf-transplantable rat mammary adenocarcinoma, is strongly suppressed by glucocorticoid hormones. hybrids were formed between glucocorticoid-suppressible con8.hd6 mammary tumor cells (con8 transfected with the histidinol dehydrogenase selectable marker) and either glucocorticoid-resistant 8ruv7 mammary tumor cells (derived from con8) or mct-htc rat hepatoma cells. both of the glucocorticoid-resistant 8ruv7 a ...19911933866
evaluation of the role of ligand and thermal activation of specific dna binding by in vitro synthesized human glucocorticoid receptor.we have used a dna-binding/immunoprecipitation assay to analyze the capacity of human glucocorticoid receptor (hgr), generated in rabbit reticulocyte lysates, to bind dna. in vitro translated hgr was indistinguishable from native hgr, as determined by migration on sodium dodecyl sulfate-polyacrylamide gels, sedimentation on sucrose density gradients, and reactivity with antipeptide antibodies generated against hgr. in addition, cell-free synthesized hgr was capable of specific binding to glucoco ...19911944294
selective depletion in hiv infection of t cells that bear specific t cell receptor v beta sequences.the mechanism of t cell depletion during infection with the human immunodeficiency virus (hiv) is unclear. examination of the repertoire of t cell receptor v (variable) regions in persons infected with hiv revealed the absence of a common set of v beta regions, whereas v alpha usage was normal. the lack of these v beta segments did not appear to correlate with opportunistic infections. the selective elimination of t cells that express a defined set of v beta sequences may indicate the presence o ...19911948066
a glucocorticoid response element enhances transcription of a methionine trna gene in cis and trans.in vitro transcription experiments using a xenopus laevis cell-free extract have demonstrated that a dna fragment containing a glucocorticoid response element (gre) significantly enhances the expression of a methionine trna gene. this stimulation can be observed when the element is located in cis or trans. in the cis configuration, the element can be located 2900 basepairs from the gene and still display transcriptional enhancement. in trans, the enhancement can occur at a low element to templat ...19901963472
structural determinants of a glucocorticoid receptor recognition element.analysis of the relative inducibility of an extensive series of mutant glucocorticoid response elements (gres) defines features critical to the constitution of an active gre. assuming that function as a gre reflects binding of glucocorticoid receptor, our activity data are consistent with the recognition of the gre as two hexamer half-sites, each half-site recognized by a single subunit of a receptor dimer, probably in a cooperative fashion. integrity of both half-sites is necessary for an activ ...19901964489
characterization of int-2: a member of the fibroblast growth factor family.int-2 was discovered as a proto-oncogene transcriptionally activated by mmtv proviral insertion during mammary tumorigenesis in the mouse. sequence analysis showed int-2 to be a member of the fibroblast growth factor family of genes. in normal breast and most other adult mouse tissues, int-2 expression was not detected except for low levels in brain and testis. however, using in situ hybridization, expression was found at a number of sites during embryonic development, from day 7 until birth. an ...19901964688
association of hst gene expression with metastatic phenotype in mouse mammary tumors.from the pregnancy-dependent mouse mammary tumor tpdmt-4, four autonomous sublines were established after its independent progression under different conditions. despite their similar growth rates in inguinal fat pads, three sublines formed lung metastases, and one did not when they were injected i.v. into mice as a single cell suspension. the tpdmt-4 tumor and the nonmetastatic subline expressed mrna for the orf gene of mouse mammary tumor virus, whereas all metastatic sublines did not. this su ...19901964796
inducible expression of herpes simplex virus type 1 glycoprotein c in nih 3t3 cells.antibodies directed against the glycoprotein c (gc) of herpes simplex virus type 1 (hsv-1) are known to be mainly hsv-1-specific, whereas antibodies against other major hsv-1 glycoproteins cross-react with hsv-2 antigens. to investigate the immunological features of gc-1, the gene encoding gc-1 was isolated and cloned from dna of cells infected with hsv-1. the 3.6 kbp sali fragment r of hsv-1 dna was modified in order to place the gene under transcriptional control of the glucocorticoid dependen ...19901965287
the order of processing events in mouse mammary tumor virus envelope protein maturation: implications for the location of the glucocorticoid-regulated step.treatment of the w7mg1 mouse t lymphoma cell line with glucocorticoid stimulates directly or indirectly two observable steps in the processing of mouse mammary tumor virus (mmtv) envelope glycoprotein precursor pr74: cleavage of pr74 to yield the mature glycoprotein products gp52 and gp33, and processing of the n-linked oligosaccharides to endoglycosidase h (endo h)-resistant forms found on the mature products but not on the precursor. therefore, the primary hormone-regulated event in this pathw ...19901965884
translational frameshift suppression in mouse mammary tumor virus and other retroviruses.retroviruses, related retroposons, and several rna viruses use translational frameshifting in the expression of their polymerase genes. we use retroviruses, particularly mouse mammary tumor virus, to illustrate the model which reflects our current understanding of these site-specific frameshifting events. the model has two components, a shifty sequence that facilitates ribosome slippage, and a second signal, either rna secondary structure or an unfilled ribosomal a site, that stalls the ribosome ...19901966844
a glucocorticoid-resistant rat hepatoma cell variant contains functional glucocorticoid receptor.the mechanism of glucocorticoid resistance was studied in a rat hepatoma cell variant (6.10.2) which contains low levels of glucocorticoid receptor. these cells seem to have lost glucocorticoid-induced transcriptional responses as measured by the induction of expression of stably integrated mouse mammary tumor virus gene and the endogenous tyrosine aminotransferase gene, as well as the transcriptional suppression of glucocorticoid receptor gene expression. however, characterization of the glucoc ...19901970570
prolactin effects on the dietary regulation of mouse mammary tumor virus proviral dna expression.chronic energy-intake restriction inhibits mouse mammary tumor virus (mmtv)-induced mammary tumors in c3h/ou mice by greater than 90%. we have shown that associated with suppression of mammary tumorigenesis there is a reduction or inhibition of circulating prolactin, mmtv particles expressed, and mmtv mrna transcription in mammary glands (and in most organs tested). to understand the concerted action of prolactin, energy-consumption level, and mmtv on inducing mammary tumors, experiments were de ...19901975696
acquired expression of hst-1 in an autonomous subline (chiba subline 2) derived from androgen-responsive mouse mammary tumor (shionogi carcinoma 115).since growth of shionogi carcinoma 115 (sc 115) and its autonomous subline (cs 2) were regulated by fibroblast growth factor-like peptide, expression of int-2 and hst-1 was examined in these cell lines. hybridization of genomic dna with long terminal repeat of mouse mammary tumor virus (mmtv) revealed the same pattern of restriction fragments, showing the same integration of mmtv. although weak expression of int-2 was noticed in the two cells, clear expression of hst-1 was seen only in cs 2 cult ...19901976117
a congenic line of the ddd mouse strain, ddd/1-mtv-2/mtv-2: establishment and mammary tumorigenesis.a single dominant gene on chromosome 18, mtv-2, controls both the early appearance of mammary tumors and expression of mouse mammary tumor virus (mmtv) in the milk. a congenic ddd mouse strain, ddd/1-mtv-2/mtv-2 (ddd-mtv-2), was developed by introducing this gene from grs/ajms (gr) into ddd/1 mice by repeating 12 backcrosses and subsequent inbreeding using mammary tumors as a marker for selection. southern blot analysis of the liver dna from the resulting congenic mice with ecori and mmtv-u3 pro ...19901976120
glucocorticoids locally disrupt an array of positioned nucleosomes on the rat tyrosine aminotransferase promoter in hepatoma cells.transcriptional activation by steroid hormones is often associated with the appearance of a dnase i hypersensitive site resulting from a local alteration of the nucleoprotein structure of the promoter. for the mouse mammary tumor virus long terminal repeat, a viral promoter under glucocorticoid control, a model has been proposed: the appearance of the hormonodependent dnase i hypersensitive site reflects the displacement of a single precisely positioned nucleosome associated with the glucocortic ...19901979170
transcriptional activation and nuclear targeting signals of the human androgen receptor.the androgen receptor (ar) is a signal-transducing protein required for sexual differentiation, development, and expression of the male phenotype. a series of human ar deletion mutants were created either by site-directed mutagenesis using restriction enzyme digestion, the polymerase chain reaction, or, for a series of unidirectional nh2-terminal deletions, exonuclease iii digestion. receptor mutants were expressed in monkey kidney cos cells as truncated ar proteins between 20 and 107 kda as rev ...19911985913
long terminal repeats of dwarf hamster endogenous retrovirus are highly diverged and do not maintain efficient transcription.recently we described a new endogenous proretrovirus of dwarf hamster phodopus sungorus (mrs-ps). its sequence possesses evident homology with the endonuclease domain of the mouse mammary tumor virus pol gene. here we present nucleotide sequence data on three clones of retroviral long terminal repeats. as many as 15% of substituted, deleted, and inserted base pairs were found while comparing these sequences. hence, mrs-ps seems to be rather an old genetic element which originated about 30 millio ...19911994585
interaction of androgen response elements with the dna-binding domain of the rat androgen receptor expressed in escherichia coli.a fragment of the rat androgen receptor (amino acids 533-637) containing the dna-binding domain was produced in escherichia coli as a fusion product with protein a of staphylococcus aureus. the fusion protein was purified on igg-sepharose, a method that does not involve the use of denaturing agents. approximately 4 mg of fusion protein was obtained from 500 ml of bacterial culture. in gel shift assays, the recombinant dna-binding domain displays an affinity for a fragment of the long terminal re ...19911995608
decreased glucocorticoid receptor activity following glucocorticoid receptor antisense rna gene fragment transfection.depression is often characterized by increased cortisol secretion caused by hyperactivity of the hypothalamic-pituitary-adrenal axis and by nonsuppression of cortisol secretion following dexamethasone administration. this hyperactivity of the hypothalamic-pituitary-adrenal axis could result from a reduced glucocorticoid receptor (gr) activity in neurons involved in its control. to investigate the effect of reduced neuronal gr levels, we have blocked cellular gr mrna processing and/or translation ...19911996114
synergism between steroid response and promoter elements during cell-free transcription.we have analyzed quantitatively the influence of distal promoter elements on steroid-responsive gene expression in vitro. functional synergism between enhancer and distal promoter elements was examined using two model promoters, one containing a natural promoter (mouse mammary tumor virus long terminal repeat) and one constructed artificially. human glucocorticoid receptor (gr) expressed in baculovirus induces transcription from a mouse mammary tumor virus long terminal repeat-containing dna tem ...19912005127
lovastatin selectively inhibits ras activation of the 12-o-tetradecanoylphorbol-13-acetate response element in mammalian cells.to evaluate ras-mediated signal transduction, an alkaline phosphatase gene (seap) was placed under the control of the ras-inducible phorbol ester response element (tre) in murine fibroblasts (tre-seap cells). the kirsten ras gene was placed under the control of the glucocorticoid-inducible mouse mammary tumor virus promoter and introduced into the tre-seap cells. dexamethasone increased ras expression in the tre-seap cells carrying the kirsten ras gene and stimulated seap activity 25-fold. lavos ...19912005914
transcriptional control by nuclear receptors.gene regulation by steroid hormones is accomplished by a variety of different mechanisms leading to induction or repression of particular genes. these mechanisms are all mediated by a single class of intracellular hormone receptors, which in the unliganded state are maintained in an inactive form by association with other cellular proteins, including hsp90. induction of the mouse mammary tumor virus (mmtv) requires binding of the hormone receptor to a hormone-responsive element (hre) that is pre ...19912010057
polyomavirus middle tumor antigen increases responsiveness to growth factors.the middle tumor antigen (mt) of polyomavirus is unable to transform a clone of nih 3t3 cells to anchorage independence (l. raptis and j.b. bolen, j. virol. 63:753-758, 1989). however, this oncogene increased the responsiveness of these cells to the growth factors (alpha-like and beta-type transforming growth factors) produced by cells possessing the whole transforming region of polyomavirus. this resulted in the growth of nih 3t3 cells, expressing mt under control of the dexamethasone-regulatab ...19912016775
identification of two distinct nuclear factors with dna binding activity within the glucocorticoid regulatory region of the rat alpha-1-acid glycoprotein promoter.efficient glucocorticoid induction of alpha-1-acid glycoprotein (agp) mrna in rat hepatoma cells htc (jz-1) requires the activity of one or more preexisting and labile proteins acting cooperatively with the glucocorticoid receptor. inhibiting protein synthesis markedly diminishes the glucocorticoid induction of rat agp mrna without affecting the inducibility of other glucocorticoid inducible genes such as the mouse mammary tumor virus (mmtv) or tyrosine amino transferase (tat). the sequences res ...19912039514
a frame-shift mutation in the androgen receptor gene causes complete androgen insensitivity in the testicular-feminized mouse.the testicular feminized (tfm) mouse lacks completely androgen responsiveness; and therefore, is unique for studying the role of androgenic steroids in different biological processes. in order to understand the molecular basis of this mutation, 2.8 kilobases of cdna encoding the tfm mouse androgen receptor (ar) were amplified with a polymerase chain reaction (pcr) technique. no large deletion in the coding region of the tfm mouse ar was detected. however, sequence analysis revealed a single base ...19912041777
inhibition of hiv-ltr gene expression by oligonucleotides targeted to the tar element.all human immunodeficiency virus mrnas contain a sequence known as tar (trans-activating responsive sequence). the tar element forms a stable rna stem-loop structure which binds the hiv tat (trans-activator) protein and mediates increased viral gene expression. in principle, molecules which bind to the tar rna structure would inhibit trans-activation by perturbing the native rna secondary structure. we have constructed a series of phosphodiester and phosphorothioate antisense oligonucleotides wh ...19912062653
concerted stimulation of transcription by glucocorticoid receptors and basal transcription factors: limited transcriptional synergism suggests mediation by coactivators/adaptors.steroid receptors have been reported to stimulate transcription in a manner synergistic with other transcription factors. we have examined this synergism or functional cooperativity between glucocorticoid receptors and basal transcription factors in a variety of promoter and reporter gene contexts. a fragment containing a hormone response element from mouse mammary tumor virus was fused to well characterized promoters from the herpes virus thymidine kinase and mouse beta-globin genes and to rela ...19912072921
oncogene n-ras mediates selective inhibition of c-fos induction by nerve growth factor and basic fibroblast growth factor in a pc12 cell line.a cell line was generated from u7 cells (a subline of pc12 rat pheochromocytoma cells) that contains a stably integrated transforming mouse n-ras (lys-61) gene under the control of the long terminal repeat from mouse mammary tumor virus. such cells, designated ur61, undergo neuronal differentiation upon exposure to nanomolar concentrations of dexamethasone, as a consequence of expression of the activated n-ras gene (i. guerrero, a. pellicer, and d.e. burstein, biochem, biophys. res. commun. 150: ...19902108319
effect of a dominant inhibitory ha-ras mutation on mitogenic signal transduction in nih 3t3 cells.we used a dominant inhibitory mutation of c-ha-ras which changes ser-17 to asn-17 in the gene product p21 [p21(asn-17)ha-ras] to investigate ras function in mitogenic signal transduction. an nih 3t3 cell line [nih(m17)] was isolated that displayed inducible expression of the mutant ha-ras gene (ha-ras asn-17) via the mouse mammary tumor virus long terminal repeat and was growth inhibited by dexamethasone. the effect of dexamethasone induction on response of quiescent nih(m17) cells to mitogens w ...19902118993
overexpression of a partial human androgen receptor in e. coli: characterization of steroid binding, dna binding, and immunological properties.the recent cloning of human androgen receptor (ar) cdnas in this and other laboratories has provided valuable probes for investigating the structure and function of the ar at the molecular level. we now report the overexpression of a region of the human ar containing both the dna- and hormone-binding domains in e. coli, which provides a means to produce large amounts of ar for analysis and use in functional studies. under isopropyl-beta-d-thiogalactopyranoside induction, a tripartite protein, co ...19902127955
secreted int-1 protein is associated with the cell surface.the murine int-1 proto-oncogene has been implicated in neural development and, when transcriptionally activated by mouse mammary tumor virus, contributes to the genesis of mammary tumors. to understand the function of the int-1 gene product in these processes, we have characterized the biochemical properties of int-1 protein expressed in a neuroendocrine cell line transfected with int-1 cdna. here we provide evidence that int-1 protein is secreted and associates with the cell surface. int-1 prot ...19902140430
negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53.to investigate the effect that human wild-type p53 (wt-p53) expression has on cell proliferation we constructed a recombinant plasmid, pm47, in which wt-p53 cdna is under transcriptional control of the hormone-inducible mouse mammary tumor virus promoter linked to the dominant biochemical selection marker gene eco gpt. the pm47 plasmid was introduced into t98g cells derived from a human glioblastoma multiforme tumor, and a stable clonal cell line, gm47.23, was derived that conditionally expresse ...19902143581
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