| the extracellular region of heregulin is sufficient to promote mammary gland proliferation and tumorigenesis but not apoptosis. | heregulin (hrg) is a member of the neuregulin family of ligands that have been shown to interact with and activate erbb receptors. a transgenic mouse model in which full-length hrg is overexpressed has proven that this protein can induce carcinomas in the murine mammary gland. these tumors display a high level of apoptosis, which appears to be mediated by the cytoplasmic domain of hrg. because both proliferation and apoptosis play a role in tumor formation, we wished to separately view those per ... | 2000 | 10919660 |
| breaking tolerance to a tumor-associated viral superantigen as a basis for graft-versus-leukemia reactivity. | a major goal in tumor immunotherapy consists of breaking potential tumor-specific t-cell unresponsiveness (tolerance), which may explain tumor growth in cancer patients. we report that immunological tolerance to a tumor-associated viral superantigen (sag) is overcome in a mouse lymphoma model by transfer of allogeneic t cells expressing sag-reactive vbeta6 t-cell receptor chains. surprisingly, upon contact with sag-expressing lymphoma cells, vbeta6 t cells became activated rather than tolerized ... | 2000 | 10925364 |
| blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in mmtv/neu + mmtv/tgf-alpha bigenic mice. | overexpression of erbb-2/neu has been causally associated with mammary epithelial transformation. here we report that blockade of the epidermal growth factor receptor (egfr) kinase with ag-1478 markedly delays breast tumor formation in mouse mammary tumor virus (mmtv)/neu + mmtv/transforming growth factor alpha bigenic mice. this delay was associated with inhibition of egfr and neu signaling, reduction of cyclin-dependent kinase 2 (cdk2) and mitogen-activated protein kinase (mapk) activities and ... | 2000 | 10931950 |
| the mouse mammary tumor virus transcription enhancers for hematopoietic progenitor and mammary gland cells share functional elements. | expression of mouse mammary tumor virus (mmtv)-encoded superantigens in b lymphocytes is required for viral transmission and pathogenesis. we have previously established a critical role of an enhancer element within the long terminal repeat (ltr) for mmtv sag gene expression in b-lymphoid progenitor cells. we now demonstrate enhancer activity of this element in a promyelocytic progenitor cell line. we also map the position of the enhancer within the u3 region of the mmtv ltr and show that the pr ... | 2000 | 10933730 |
| structure and dynamic properties of a glucocorticoid receptor-induced chromatin transition. | activation of the mouse mammary tumor virus (mmtv) promoter by the glucocorticoid receptor (gr) is associated with a chromatin structural transition in the b nucleosome region of the viral long terminal repeat (ltr). recent evidence indicates that this transition extends upstream of the b nucleosome, encompassing a region larger than a single nucleosome (g. fragoso, w. d. pennie, s. john, and g. l. hager, mol. cell. biol. 18:3633-3644). we have reconstituted mmtv ltr dna into a polynucleosome ar ... | 2000 | 10938123 |
| behavioral and immune changes in v-ha-ras transgenic mice. | transgenic mice (oncomice) with an activated v-ha-ras oncogene under the control of the mouse mammary tumor virus promoter develop mammary tumors. we wondered if the expression of the v-ha-ras oncogene product would induce changes in mice behavioral activity, that could be associated with alterations in their immune system. behavior was evaluated in an open field study considering line crossings and rears. oncomice consistently showed less activity than fvb mice. lieber-decarli diet decreased bo ... | 2000 | 10952035 |
| expression of mouse mammary tumor virus superantigen accelerates tumorigenicity of myeloma cells. | to investigate whether superantigen (sag) from endogenous mouse mammary tumor virus functions as an immunogenic or a tumorigenic factor in tumor development, the balb/c myeloma cell line fo was transfected with the sag gene from the 3' mtv-50 long terminal repeat (ltr) open reading frame (orf), the product of which was specific for vbeta6. all five transfectants expressing mtv-50 ltr orf mrna showed stimulatory activity for vbeta6 t-cell hybridomas in vitro; this activity was inhibited by the ad ... | 2000 | 10954519 |
| intercellular transfer of a soluble viral superantigen. | mouse mammary tumor virus (mmtv) superantigens (vsags) can undergo intercellular transfer in vivo and in vitro such that a vsag can be presented to t cells by major histocompatibility complex (mhc) class ii proteins on antigen-presenting cells (apcs) that do not express the superantigen. this process may allow t-cell activation to occur prior to viral infection. consistent with these findings, vsag produced by chinese hamster ovary (cho) cells was readily transferred to class ii ie and ia (h-2(k ... | 2000 | 10954523 |
| dynamics of gene targeting and chromatin remodelling by nuclear receptors. | activation of the murine-mammary-tumour virus (mmtv) promoter by the glucocorticoid receptor (gr) is associated with a chromatin structural transition in the b nucleosome region of the viral long terminal repeat (ltr). we have reconstituted this nucleoprotein transition with chromatin assembled on mmtv ltr dna with drosophila embryo extracts, purified gr, and hela nuclear extract. chromatin remodelling in vitro is atp-dependent and maps to a region identical with that found in vivo. we demonstra ... | 2000 | 10961929 |
| genetics of mouse mammary tumor virus-induced mammary tumors: linkage of tumor induction to the gag gene. | retroviruses are believed to induce tumors by acting as insertional mutagens that activate expression of cellular protooncogenes. indeed, almost 90% of mouse mammary tumor virus (mmtv)-induced mammary tumors in c3h/he mice show upregulation of int protooncogenes. we have analyzed three different mmtv variants [mmtv(c3h), mmtv(hej), and a genetically engineered mmtv hybrid provirus (hp)] for tumorigenicity in mice from two distinct genetic backgrounds. all three viruses were tumor causing in balb ... | 2000 | 10982330 |
| c3h mouse mammary tumor virus superantigen function requires a splice donor site in the envelope gene. | mouse mammary tumor virus (mmtv) encodes a superantigen (sag) that is required for efficient milk-borne transmission of virus from mothers to offspring. the mrna used for sag expression is controversial, and at least four different promoters (two in the long terminal repeat and two in the envelope gene) for sag mrna have been reported. to determine which rna is responsible for sag function during milk-borne mmtv transmission, we mutated a splice donor site unique to a spliced sag rna from the 5' ... | 2000 | 11000212 |
| identification of notch1 as a frequent target for provirus insertional mutagenesis in t-cell lymphomas induced by leukemogenic mutants of mouse mammary tumor virus. | in contrast to wild-type mouse mammary tumor virus (mmtv), the mmtv mutants with specific deletions in the u3 region of their long terminal repeats cause t-cell lymphomas. in 30% of t-cell lymphomas arising in balb/c mice infected with mla-mmtv, a leukemogenic mmtv mutant, we have found that mmtv proviruses were integrated into a short region of the notch1 genome, so that truncated notch1 transcripts encoding the transmembrane and the cytoplasmic domains of notch1 protein could be expressed. thu ... | 2000 | 11000255 |
| developmental role of the snf1-related kinase hunk in pregnancy-induced changes in the mammary gland. | the steroid hormones 17 beta-estradiol and progesterone play a central role in the pathogenesis of breast cancer and regulate key phases of mammary gland development. this suggests that developmental regulatory molecules whose activity is influenced by ovarian hormones may also contribute to mammary carcinogenesis. in a screen designed to identify protein kinases expressed in the mammary gland, we previously identified a novel snf1-related serine/threonine kinase, hunk (hormonally upregulated ne ... | 2000 | 11003847 |
| using genetics to probe host-virus interactions; the mouse mammary tumor virus model. | it is clear that there is genetic variation among different individuals in their susceptibility to infection by viruses and other pathogens. identification of the genes involved in conferring resistance or susceptibility to viral infection will allow us to understand both mechanisms of infection and pathogenesis and to develop reagents for treating or preventing them. because of the large number of genetically well-characterized inbred mouse strains and the ability to generate targeted germ line ... | 2000 | 11008111 |
| effects of antiandrogens on chromatin remodeling and transcription of the integrated mouse mammary tumor virus promoter. | inhibition of the ligand-activated androgen receptor (ar) by antiandrogens plays an important role in the treatment of various hyperandrogenic disorders including prostate cancer. however, the molecular mechanisms of antiandrogen activity in vivo remain unclear. in this study we analyzed the effects of cyproterone acetate (cpa), flutamide (f), and hydroxyflutamide (ohf) on transcriptional activation and chromatin remodeling of the genomically integrated mouse mammary tumor virus (mmtv) promoter. ... | 2000 | 11010820 |
| alleviation of renal disease and lymphadenopathy in mrl-fasp(lrcg)/fas(lprcg) (mr-lpr(cg)) mice neonatally infected with mouse mammary tumor virus encoding superantigen strongly reactive with tcr vbeta8.2 element. | mouse mammary tumor virus transmitted by fm mice (fm-mmtv) encodes a superantigen (sag) characterized by strong reactivity with tcr vbeta8.2 element and broad spectrum of vbeta reactivity. to investigate what effects the expression in vivo of fm-mmtv sag exhibits on the course of the disease in a lupus-prone model, mrl/mpj-fas(lprcg)/fas(lprcg) (mrl-lpr9cg) mice, neonatally fm-mmtv-infected mrl-lprcg(mmtv) and uninfected mrl-lpr(cg) mice were compared for various disease parameters. in mrl-lprcg ... | 2000 | 11016595 |
| mouse mammary tumor virus superantigen expression is reduced by glucocorticoid treatment. | expression of mouse mammary tumor virus (mmtv)-encoded superantigens in b lymphocytes are required for viral transmission and pathogenesis. due to problems with detection and quantification of the superantigen protein, most reports about the mechanism of superantigen expression from the viral sag gene rely on the quantitative analysis of putative sag mrnas. the description of multiple promoters as a source of putative sag mrna has complicated the situation even further. all conclusions about the ... | 2000 | 11017791 |
| new steps in the wnt/beta-catenin signal transduction pathway. | wnt regulates developmental and oncogenic processes through its downstream effector, beta-catenin, and a set of other intracellular regulators that are largely conserved among species. wnt family genes encode secreted glycoproteins that act as ligands for membrane receptors belonging to the frizzled family of proteins. wnt-1 originally was found as a proto-oncogene that was upregulated in tumors caused by the mouse mammary tumor virus. the drosophila homologue of wnt-1, wingless, is a segment po ... | 2000 | 11036939 |
| [expression regulation of major late promoter tripartite leader sequence in adenovirus late infection]. | to investigate the influence of adenovirus major late tripartite leader sequence on specific exportation of virus mrna in the late phase of adenovirus infection. | 1998 | 11038823 |
| conditional deletion of the bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. | bcl-x is a member of the bcl2 family and has been suggested to be important for the survival and maturation of various cell types including the erythroid lineage. to define the consequences of bcl-x loss in erythroid cells and other adult tissues, we have generated mice conditionally deficient in the bcl-x gene using the cre-loxp recombination system. the temporal and spatial excision of the floxed bcl-x locus was achieved by expressing the cre recombinase gene under control of the mmtv-ltr. by ... | 2000 | 11044408 |
| the region between amino acids 245 and 265 of the bovine leukemia virus (blv) tax protein restricts transactivation not only via the blv enhancer but also via other retrovirus enhancers. | bovine leukemia virus (blv) is associated with enzootic bovine leukosis and is closely related to human t-cell leukemia virus type 1 (htlv-1). the tax protein of blv acts through the 5' long terminal repeat (ltr) of blv and activates the transcription of blv. in this study, we amplified tax genes from blv-infected cattle using pcr. we cloned the genes and monitored the transcriptional activities of the products. seven independent mutant tax proteins, with at least one amino acid substitution bet ... | 2000 | 11069988 |
| a fission yeast homolog of int-6, the mammalian oncoprotein and eif3 subunit, induces drug resistance when overexpressed. | through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of int-6, a component of the human translation initiation factor eif3. disruption of the murine int-6 gene by mouse mammary tumor virus (mmtv) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. fission yeast int6 was shown to interact with other presumptive components of eif3 in vivo, and was present in size fra ... | 2000 | 11071922 |
| fission yeast int6 is not essential for global translation initiation, but deletion of int6(+) causes hypersensitivity to caffeine and affects spore formation. | mammalian int6 protein has been considered to be a subunit of the eukaryotic translation initiation factor, eif3. the int6 locus is also known as a common integration site of mouse mammary tumor virus (mmtv). however, the function of int6 in translation initiation and the mechanism of int6-mediated tumor induction are yet to be explored. in this study, the fission yeast, schizosaccharomyces pombe, int6(+), which is 43% identical to the mammalian counterpart, was deleted. despite the evidence tha ... | 2000 | 11071923 |
| [from gene to disease; the apc gene and familial adenomatous polyposis coli]. | familial adenomatous polyposis coli is an autosomal dominant hereditary form of colorectal cancer associated with mutations in the adenomatous polyposis coli (apc) gene on chromosome 5. the apc protein is thought to mediate the stability of beta-catenin in the wnt signaling transduction pathway ('wingless-type mouse mammary tumor virus integration site family member') in normal colonic epithelial cells, thereby indirectly regulating the expression of wnt target genes such as the c-myc-oncogene. ... | 2000 | 11072519 |
| increased immunoglobulin g, but not m, binding to endogenous retroviral antigens in hiv-1 infected persons. | the modes of interaction between products of human endogenous retroviral (herv) sequences and the immune system are largely unknown. in hiv infected persons, an exogenous retrovirus adds further complexity to the situation. therefore, 14 synthetic peptides with sequences derived from conserved regions of various endogenous retroviruses (ervs) and from related exogenous retroviruses were used to search for igg and igm antibodies that bind to such antigens in 15 hiv-1 seropositive and 17 seronegat ... | 2000 | 11074471 |
| integration of proviral sequences, but not at the common integration sites of the fgf8 locus, in an androgen-dependent mouse mammary shionogi carcinoma. | a retroviral insertional mutation, especially by mouse mammary tumor virus (mmtv), is a major cause of murine mammary tumorigenesis. prompted by our previous finding that fgf8, an insertionally activated cellular oncogene, is highly expressed in androgen-dependent mouse mammary shionogi carcinoma cells, we here investigated retroviral integration adjacent to the fgf8 locus in shionogi carcinoma. in the genomic southern blots for fgf8 and its 5'-upstream gene npm3, the hybridized fragments were i ... | 2000 | 11075944 |
| mammary tumor development in mmtv-c-myc/mmtv-v-ha-ras transgenic mice is unaffected by osteopontin deficiency. | transgenic mice expressing c-myc and v-ha-ras specifically in the mammary gland under the control of the mammary specific promoter mmtv develop unifocal mammary tumors with a half time of about 46 days, and these tumors express high levels of osteopontin mrna and protein. in order to evaluate the requirement for osteopontin expression by these tumors, we have crossed transgenic mice expressing these two oncogenes with mice with a targeted disruption of the osteopontin gene. littermates expressin ... | 2000 | 11079161 |
| non-hodgkin's lymphoma in women with breast cancer. | the purpose of this study was to describe a series of patients with breast cancer and non-hodgkin's lymphoma and to determine the usual sequence of the diagnoses. therapy for both neoplasms and its relationship to the development of the second neoplasm were also evaluated. | 2000 | 11079174 |
| effects of hiv-1 peptides on t-cell receptor variable beta chain families. | superantigens (sags) selectively stimulate expansion and then deletion of specific t cell antigen receptor (tcr) variable beta chain (vbeta) families. we investigated six synthetically produced hiv-1-related peptides for evidence of sag activity: three derived all or in part from the transmembrane gp41 protein and three from the genetic sequence of the trna binding region. the first three were chosen because they are highly immunogenic; the second three, because their genetic sequence is complet ... | 2000 | 11082512 |
| 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 ... | 1994 | 11091502 |
| 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 ... | 1994 | 11091515 |
| nh2-terminal cleavage of xenopus fibroblast growth factor 3 is necessary for optimal biological activity and receptor binding. | fibroblast growth factor 3 (fgf3) was originally identified as the mouse proto-oncogene int-2, which is activated by proviral insertion in tumors induced by mouse mammary tumor virus. to facilitate the biological characterization of the ligand, we have analyzed its homologue in xenopus laevis, xfgf3. here we confirm that the x. laevis genome contains two distinct fgf3 alleles, neither of which is capable of encoding the nh2-terminally extended forms specified by the mouse and human fgf3 genes. u ... | 2000 | 11095248 |
| requirement for reverse immune surveillance for the growth of germinal center-derived murine lymphomas. | the concept of reverse immune surveillance, first conceived over 12 years ago, described the relationship that existed between germinal center-derived b cell lymphoma cells and the host immune system in sjl/j mice. according to reverse immune surveillance, recognition of tumor cell antigens and a response by the host immune system is required for tumor growth. the phenomenon of reverse immune surveillance related to b cell lymphomas has recently also been characterized in another inbred mouse st ... | 2000 | 11100880 |
| matrix metalloproteinase 9 promoter activity is induced coincident with invasion during tumor progression. | matrix metalloproteinase 9 (mmp-9, also known as gelatinase b or 92-kd type iv collagenase) is overexpressed in many human and murine cancers. we induced carcinomas in mice carrying a transgene that links the mmp-9 promoter to the reporter ss-galactosidase so that activation of the mmp-9 promoter would be indicated by ss-galactosidase. mammary carcinomas were induced by mating the mmp-9 promoter reporter transgenic mice with mice carrying a transgene for murine mammary tumor virus promoter linke ... | 2000 | 11106549 |
| reduced expression of int-6/eif3-p48 in human tumors. | the int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (mmtv) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eif3-p48). int-6/eif3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. int-6/eif3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. viral insert ... | 2001 | 11115556 |
| ligand-activated progesterone receptor isoform hpr-a is a stronger transactivator than hpr-b for the expression of igfbp-1 (insulin-like growth factor binding protein-1) in human endometrial stromal cells. | in human endometrium, the levels of progesterone receptor (pr) isoforms hpr-a and hpr-b are differentially regulated during the reproductive cycle. progesterone significantly increases the content of hpr-a, the predominant isoform in decidualized stromal cells (1). the purpose of this study was to determine the capacity of hpr-a and hpr-b to transactivate the progestin-dependent target gene in human endometrial stromal cells. we examined the effect of cotransfection of hpr-a or hpr-b on the expr ... | 2000 | 11117526 |
| synchronous deletion of mtv-superantigen-reactive thymocytes in the cd3(medium/high) cd4(+)cd8(+) subset. | multiple model systems have demonstrated that negatively selected thymocytes can be deleted during the immature cd4(+)cd8(+) cd3(low) stage after high affinity interaction of t-cell receptors (tcrs) with antigen:major histocompatibility complex (mhc) complexes. superantigens (sags) derived from endogenous mammary tumour viruses (mtv) induce negative selection of mtv-sag-reactive thymocytes regardless of which peptide antigen is presented by mhc molecules. in this study, the timing of deletion of ... | 2000 | 11119259 |
| fission yeast homolog of murine int-6 protein, encoded by mouse mammary tumor virus integration site, is associated with the conserved core subunits of eukaryotic translation initiation factor 3. | the murine int-6 locus, identified as a frequent integration site of mouse mammary tumor viruses, encodes the 48-kda eif3e subunit of translation initiation factor eif3. previous studies indicated that the catalytically active core of budding yeast eif3 consists of five subunits, all conserved in eukaryotes, but does not contain a protein closely related to eif3e/int-6. whereas the budding yeast genome does not encode a protein closely related to murine int-6, fission yeast does encode an int-6 ... | 2001 | 11134033 |
| evaluation of in vitro methods for detecting the effects of various chemicals on the human progesterone receptor, with a focus on pyrethroid insecticides. | the progesterone receptor (pr) is associated with physiological events such as implantation and the maintenance of pregnancy. recently, it has become a social concern that chemicals may exert agonistic or antagonistic effects on hormone receptors. therefore, we examined the effects of various chemicals on the human pr, with a focus on pyrethroid insecticides, using three in vitro methods. eight pyrethroid insecticides (fenvalerate, d-allethrin, d-phenothrin, prallethrin, empenthrin, permethrin, ... | 2001 | 11137321 |
| a reduction in blood insulin levels as a host endocrine response during tumor development. | it has been previously reported that endogenous insulin levels decrease during tumor growth. we have now studied whether this host endocrine response is independent of the way in which the tumor is induced. for this purpose, animals transplanted with tumor cells induced by 3-methylcholanthrene (mca) or 7,12-dimethylbenz(a) anthracene (dmba), or with el-4 lymphoma cells, and animals that develop autochthonous tumors induced by mca or the murine mammary tumor virus (mmtv) were used. these procedur ... | 2000 | 11137618 |
| mechanisms of retrovirus-induced oncogenesis. | retroviruses are implicated in a series of human and animal tumours such as leukaemias, mammary tumours or skin cancer. the mechanism that they use to induce tumour formation varies. insertional mutagenesis is a common mechanism in rodent, feline and avian retroviruses, where the retrovirus integrates into the host genome and affects the transcription of the neighbouring genes. cloning of these affected genes led to identification of a series of oncogenes that play a significant role in the indu ... | 2000 | 11140855 |
| the glucocorticoid receptor and stat6 physically and functionally interact in t-lymphocytes. | in lymphocytes, glucocorticoids (gc)- and interleukin-4-signaling pathways are known to interact, as evidenced by inhibition of il-4-mediated proliferation by dexamethasone or suppression of gc-induced apoptosis by il-4. in this study, we characterized the molecular basis for this reciprocal interference. we report that, in murine ctll-2 cells, il-4 inhibits gc-induced mmtv (mouse mammary tumor virus) promoter transactivation, and that gc suppress il-4-induced transactivation of a stat6 (signal ... | 2000 | 11150515 |
| derivation and initial characterization of a mouse mammary tumor cell line carrying the polyomavirus middle t antigen: utility in the development of novel cancer therapeutics. | here we describe the derivation of novel cell lines from spontaneous mammary tumors that arose in mouse mammary tumor virus-polyomavirus (mmtv-pyv) middle t (midt) transgenic mice. clonal cell lines from four mixed cell populations were tested for adenovirus transducibility and sensitivity to p53 tumor suppressor gene therapy mediated by sch58500, a replication-deficient adenovirus that expresses human p53. the midt2-1 cell line was selected for further characterization in vitro and in vivo. thi ... | 2000 | 11156413 |
| diverse repertoire of the mhc class ii-peptide complexes is required for presentation of viral superantigens. | among other features, peptides affect mhc class ii molecules, causing changes in the binding of bacterial superantigens (b-sag). whether peptides can alter binding of viral superantigens (v-sag) to mhc class ii was not known. here we addressed the question of whether mutations limiting the diversity of peptides bound by the mhc class ii molecules influenced the presentation of v-sag and, subsequently, the life cycle of the mouse mammary tumor virus (mmtv). t cells reactive to v-sag were found in ... | 2001 | 11160278 |
| type b leukemogenic virus has a t-cell-specific enhancer that binds aml-1. | type b leukemogenic virus (tblv) induces rapidly appearing t-cell tumors in mice. tblv is highly related to mouse mammary tumor virus (mmtv) except that tblv long terminal repeats (ltrs) have a deletion of negative regulatory elements and a triplication of sequences flanking the deletion. to determine if the ltr triplication represents a viral enhancer element, we inserted the triplication upstream and downstream in either orientation relative to the thymidine kinase promoter linked to the lucif ... | 2001 | 11160721 |
| serum antibodies reactive with non-human primate retroviruses identified in acute onset schizophrenia. | schizophrenia is a pervasive neuropsychiatric disease of uncertain etiology. previous studies have postulated that retroviruses may contribute to the etiology of some cases of schizophrenia. we examined the possible relationship between retroviral infection and schizophrenia by measuring antibodies to a number of different primate retroviruses in the sera of individuals undergoing their first hospitalization for this disease. sera from patients with first onset schizophrenia and matched healthy ... | 2000 | 11175321 |
| c-myc induces mammary tumorigenesis by means of a preferred pathway involving spontaneous kras2 mutations. | although the process of mammary tumorigenesis requires multiple genetic events, it is unclear to what extent carcinogenesis proceeds through preferred secondary pathways following a specific initiating oncogenic event. similarly, the extent to which established mammary tumors remain dependent on individual mutations for maintenance of the transformed state is unknown. here we use the tetracycline regulatory system to conditionally express the human c-myc oncogene in the mammary epithelium of tra ... | 2001 | 11175856 |
| green tea polyphenols as potent enhancers of glucocorticoid-induced mouse mammary tumor virus gene expression. | the effect of natural and synthetic galloyl esters on glucocorticoid-induced gene expression was evaluated by using rat fibroblast 3y1 cells stably transfected with a luciferase reporter gene under the transcriptional regulation of the mouse mammary tumor virus promoter. the glucocorticoid-induced gene transcription was strongly suppressed by synthetic alkyl esters; n-dodecyl gallate showed the most potent inhibition (66% inhibition at 10 microm), which was far more potent than that of crude tan ... | 2001 | 11178969 |
| normal pathogen-specific immune responses mounted by ctla-4-deficient t cells: a paradigm reconsidered. | ctla-4 is a critical negative regulator of t cell responses and ctla-4-deficient (ctla-4(-/-)) mice die of a lymphproliferative disease. nevertheless, rag-2-deficient mice reconstituted with a mixture of ctla-4(-/-) and normal (ctla-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their t cells do not express ctla-4. using such mixed chimeras, we analyzed the role of ctla-4 in specific t cell responses to lymphocytic choriomeningitis virus, leishmania major and ... | 2001 | 11180109 |
| changing responsiveness to chemokines allows medullary plasmablasts to leave lymph nodes. | during t cell-dependent antibody responses lymph node b cells differentiate either to plasmablasts that grow in the medullary cords, or to blasts that proliferate in follicles forming germinal centers. many plasmablasts differentiate to plasma cells locally, but some leave the medullary cords and migrate to downstream lymph nodes. to assess the basis for this migration, changes in the responsiveness of b cells to a range of chemokines have been studied as they differentiate. naive b cells expres ... | 2001 | 11180126 |
| cloning and in vitro characterization of alpha 1(i)-collagen 11 beta-hydroxysteroid dehydrogenase type 2 transgenes as models for osteoblast-selective inactivation of natural glucocorticoids. | the nad-dependent enzyme, 11beta-hydroxysteroid dehydrogenase type ii (11 beta hsd2), catalyzes the unidirectional conversion of biologically active glucocorticoids to inactive metabolites. in vivo, 11 beta hsd2 protects the mineralocorticoid receptor from activation by glucocorticoids in mineralocorticoid target tissues such as kidney. the goal of the present study was to use targeted overexpression of 11 beta hsd2 as a novel means of disrupting glucocorticoid signaling in osteoblastic cells. r ... | 2001 | 11181553 |
| role of promyelocytic leukemia (pml) protein in tumor suppression. | the promyelocytic leukemia (pml) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (raralpha) gene in the vast majority of acute promyelocytic leukemia (apl) patients as a consequence of chromosomal translocations. the pmlraralpha oncoprotein is thought to antagonize the function of pml through its ability to heterodimerize with and delocalize pml from the nuclear body. in apl, this may be facilitated by the red ... | 2001 | 11181703 |
| [new discoveries in experimental cancer]. | this 7th international symposium organized by the national academy of medicine on new directions in cancer management, was sponsored by iucc (international union against cancer) and received important financial assistance from the fritz bender foundation. in 1996 and 97, the first two symposia also dealt with cancer, specifically with tumor immunology and with the relation of human breast cancer with mmtv (murine mammary tumor virus). the aim of these introductory remarks is to emphasize recent ... | 2000 | 11188923 |
| superantigen disruption of cd8+ t and b lymphocyte homeostasis. | superantigens (sags) activate th cells and induce their differentiation into cytokine-producing effector cells. supranormal cytokine production is characteristic of sag-induced polyclonal th activation. study of this interaction has focused upon th cell function to the relative exclusion of other lymphocyte populations. sags also impact cells dependent upon th cells for their differentiation and disrupt the normal homeostasis of the immune system. in this report, several changes in lymphocyte bi ... | 2000 | 11205378 |
| association of mouse mammary tumor virus superantigen with mhc class ii during biosynthesis. | mouse mammary tumor viruses encode superantigens that interact with mhc class ii proteins and stimulate t cells. we show here that presentation of mouse mammary tumor virus superantigen does not require dm. furthermore, we have identified a strong class ii peptide binding motif in the mtv-7 superantigen, and we show that this motif is necessary for association with class ii molecules in in vitro translation and in vivo functional assays. our results suggest that endogenously synthesized viral su ... | 2001 | 11207286 |
| overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice. | to investigate the role of membrane-type matrix metalloproteinase-1 (mt1-mmp) in mammary gland development and tumorigenesis, transgenic mice overexpressing mt1-mmp in mammary gland under the control of the mouse mammary tumor virus long terminal repeat-promoter were generated. the mouse mammary tumor virus/mt1-mmp transgenic mice displayed abnormalities in 82% of female mammary glands. the abnormalities were verified as lymphocytic infiltration, fibrosis, hyperplasia, alveolar structure disrupt ... | 2001 | 11221894 |
| search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals. | we have reported previously that a 660-bp sequence homologous to the env gene of the mouse mammary tumor virus, but not to the known endogenous retroviruses, was present in 38% of human breast cancers (y. wang et al., cancer res., 55: 5173-5179, 1995). a unique 250-bp internal sequence was equally present in formalin-fixed breast carcinoma. it was not detected in normal human breasts or in other tumors. in this study, we have investigated whether this 250-bp env sequence was also present in the ... | 2001 | 11234880 |
| clinical and endoscopic aspects in the evolution of patients with bleeding peptic ulcer--a cohort study. | bleeding ulcers are a major problem in public health and represent approximately half of all the cases of upper gastrointestinal hemorrhage in the united states. this study aims to determine the prognostic value of factors such as clinical history, laboratory and endoscopic findings in the occurrence of new episodes of bleeding in patients who have upper gastrointestinal hemorrhage caused by gastric or duodenal peptic ulcer. | 2000 | 11236268 |
| activation of akt (protein kinase b) in mammary epithelium provides a critical cell survival signal required for tumor progression. | activation of akt by the phosphatidylinositol 3'-oh kinase (pi3k) results in the inhibition of proapoptotic signals and the promotion of survival signals (l. p. kane et al., curr. biol. 9:601-604, 1999; g. j. kops et al., nature 398:630-634, 1999). evidence supporting the importance of the pi3k/akt signaling pathway in tumorigenesis stems from experiments with transgenic mice bearing polyomavirus middle t antigen under the control of the mouse mammary tumor virus long terminal repeat promoter. m ... | 2001 | 11238953 |
| identification of a proviral structure in human breast cancer. | involvement of a virus similar to mouse mammary tumor virus (mmtv) in human breast cancer has long been postulated but never demonstrated. we have detected by pcr a 660-bp sequence similar to the env gene of mmtv but not to the known endogenous viruses, in 38% of human breast cancers examined (wang et al., cancer res., 55: 5173-5179, 1995). this sequence was expressed in 66% of the env-positive tumors as detected by reverse transcription-pcr (wang et al., clin. cancer res., 4: 2565-2568, 1998). ... | 2001 | 11245493 |
| mouse models for breast cancer. | | 1999 | 11250684 |
| tyrosine kinase signalling in breast cancer: fibroblast growth factors and their receptors. | the fibroblast growth factors [fgfs (murine), fgfs (human)] constitute a large family of ligands that signal through a class of cell-surface tyrosine kinase receptors. fgf signalling has been associated in vitro with cellular differentiation as well as mitogenic and motogenic responses. in vivo, fgfs are critical for animal development, and some have potent angiogenic properties. several fgfs have been identified as oncogenes in murine mammary cancer, where their deregulation is associated with ... | 2000 | 11250709 |
| mmtv-like env gene sequences in human breast cancer. | we have previously detected an mmtv env gene-like 660 bp sequence in 38% of human breast cancers, but not in normal tissues or other tumors. in this communication we report the sequences from eleven tumors and three breast cancer cell lines, and compare them to four strains of mmtv and to the known endogenous retroviral sequences. the breast cancer sequences were highly homogenous to the mmtv's, but not to the endogenous sequences suggesting an exogenous origin. | 2001 | 11266212 |
| transgenic muc1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland. | muc1 is a large (>400 kda), heavily glycosylated transmembrane protein that is aberrantly expressed on greater than 90% of human breast carcinomas and subsequent metastases. the precise function of muc1 overexpression in tumorigenesis is unknown, although various domains of muc1 have been implicated in cell adhesion, cell signaling, and immunoregulation. stimulation of the mda-mb-468 breast cancer line as well as mouse mammary glands with epidermal growth factor results in the co-immunoprecipita ... | 2001 | 11278868 |
| glucocorticoids suppress human immunodeficiency virus type-1 long terminal repeat activity in a cell type-specific, glucocorticoid receptor-mediated fashion: direct protective effects at variance with clinical phenomenology. | glucocorticoid administration and/or excess secretion have been associated with increased human immunodeficiency virus type-1 (hiv-1) replication and aids progression. the hiv-1 long terminal repeat (ltr) promoter contains glucocorticoid-responsive element (gre)-like sequences that could mediate a positive effect of glucocorticoids on hiv-1. in addition, we recently demonstrated that the hiv-1 accessory protein vpr is a potent coactivator of the glucocorticoid receptor, which, like the host coac ... | 2000 | 11282284 |
| up-regulation of muc1 in mammary tumors generated in a double-transgenic mouse expressing human muc1 cdna, under the control of 1.4-kb 5' muc1 promoter sequence and the middle t oncogene, expressed from the mmtv promoter. | in this study we examined the regulation of expression of the human muc1 gene in vivo, by developing muc1 transgenic mice. the data showed that epithelial-specific expression of muc1 can be directed by just 1.4 kb of 5' flanking sequence using muc1 cdna as a reporter gene in vivo. furthermore, high levels of muc1 expression were seen in the lactating mammary gland and in spontaneous mammary tumors generated by crossing the muc1 transgenics with mice transgenic for the polyoma middle t oncogene u ... | 2001 | 11291075 |
| detection of mmtv-like ltr and ltr-env gene sequences in human breast cancer. | we have previously reported, using the polymerase chain reaction (pcr), the presence of a 660 bp sequence homologous to the env gene of mmtv in 38% of the human breast cancers studied, but not in normal breasts nor in other tumors or tissues. we have now investigated the presence of mmtv-like ltr sequences in human breast cancer and normal breast tissue. primers were selected to amplify a 630 bp sequence homologous to mmtv, but not to the endogenous retrovirus herv-k10. this sequence was detecte ... | 2001 | 11295054 |
| functional plasticity of the lack-reactive vbeta4-valpha8 cd4(+) t cells normally producing the early il-4 instructing th2 cell development and susceptibility to leishmania major in balb / c mice. | early production of il-4 by lack-reactive vbeta4-valpha8 cd4(+) t cells instructs aberrant th2 cell development and susceptibility to leishmania major in balb / c mice. this was demonstrated using vbeta4(+)-deficient balb / c mice as a result of chronic infection with mmtv (sim), a mouse mammary tumor virus expressing a vbeta4-specific superantigen. the early il-4 response was absent in these mice which develop a th1 response to l. major. here, we studied the functional plasticity of lack-reacti ... | 2001 | 11298356 |
| glucocorticoid hormone-induced receptor localization to the chromatin fibers formed on injected dna in xenopus oocytes. | oocytes from xenopus laevis have provided a model system for studying the dynamic changes that occur in chromatin during gene activation. we have reconstituted glucocorticoid receptor (gr) induced transcription from the mouse mammary tumor virus (mmtv) promoter by intranuclear injection of an mmtv-driven reporter and cytoplasmic injection of synthetic mrna(gr) into xenopus oocytes. here we investigate the intranuclear distribution of injected dna, which is assembled into chromatin. we show that ... | 2001 | 11302698 |
| impairment of mammary lobular development induced by expression of tgfbeta1 under the control of wap promoter does not suppress tumorigenesis in mmtv-infected transgenic mice. | it has previously been shown that transgenic female mice expressing tgfbeta1 under control of regulatory elements of the whey-acidic protein (wap) gene were unable to lactate. this was due to the increased apoptosis of the cells committed to the lobular-lactogenic phenotype. our goal was to determine whether the expression of wap-tgfbeta1 transgene could inhibit mmtv (mouse mammary tumor virus) tumorigenic activity in the mammary gland. it is well known that the infection with this virus produce ... | 2001 | 11304693 |
| meta-controlled env-initiated transcripts encoding superantigens of murine mtv29 and mtv7 and their possible role in b cell lymphomagenesis. | spontaneous germinal center (gc)-derived b cell lymphomas of sjl mice (rcs) transcribe a 1.8-kb mtv-29 mrna under control of the meta-env promoter. the encoded vsag29 stimulates syngeneic vbeta16(+) cd4(+) t cells, thereby acquiring t cell help necessary for rcs growth. other strains of b cell lymphoma-prone mice include mtv29(+) c57l and ma/myj, and the mtv29(-) mtv7(+)-recombinant inbred strain, sw x j-1. the lymphomas of these mice produce similar mouse mtv-vsag-encoding mrna, as characterize ... | 2001 | 11313379 |
| inhibition of mammary epithelial apoptosis and sustained phosphorylation of akt/pkb in mmtv-igf-ii transgenic mice. | igf-ii is a growth factor implicated in human cancers and animal tumor models. while the mitogenic properties of igf-ii are well documented, its ability to suppress apoptosis in vivo has never been proven. we generated independent mmtv-igf-ii transgenic mice to examine the control of epithelial apoptosis at the morphological, cellular and molecular levels during the physiological event of postlactation mammary involution. transgenic igf-ii expression was achieved in mammary epithelium and increa ... | 2001 | 11313699 |
| abnormal ornithine decarboxylase activity in transgenic mice increases tumor formation and infertility. | a transgenic mouse line carrying ornithine decarboxylase cdna as the transgene under the control of a mouse mammary tumor virus long terminal repeat (mmtv ltr) promoter was generated in order to study whether ornithine decarboxylase transgene expression will have any physiological or pathological effect during the entire life of a transgenic mouse. the high frequency of infertile animals and the loss of pups made the breeding of homozygous mice unsuccessful. however, a colony of heterozygous tra ... | 2001 | 11331206 |
| delta n89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland. | to investigate the role of beta-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of beta-catenin lacking the nh(2)-terminal 89 amino acids (delta n 89 beta-catenin) under the control of the mouse mammary tumor virus long terminal repeat. our results show that delta n 89 beta-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. virgin delta n 89 beta-catenin mammary ... | 2001 | 11331306 |
| requirement for a complex array of costimulators in the negative selection of autoreactive thymocytes in vivo. | autoreactive thymocytes can be deleted at an immature stage of their development by ag-induced apoptosis or negative selection. in addition to ag, negative selection also requires costimulatory signals from apc. we recently used a fetal thymus organ culture system to show that cd5, cd28, and tnf cooperatively regulate deletion of autoreactive thymocytes. although these experiments provided strong evidence for the action of several costimulators in negative selection, we wished to demonstrate a r ... | 2001 | 11342622 |
| extrafollicular plasmablast b cells play a key role in carrying retroviral infection to peripheral organs. | b cells can either differentiate in germinal centers or in extrafollicular compartments of secondary lymphoid organs. here we show the migration properties of b cells after differentiation in murine peripheral lymph node infected with mouse mammary tumor virus. naive b cells become activated, infected, and carry integrated retroviral dna sequences. after production of a retroviral superantigen, the infected b cells receive cognate t cell help and differentiate along the two main differentiation ... | 2001 | 11342650 |
| superantigens: the good, the bad, and the ugly. | increasing evidence suggests that superantigens play a role in immune-mediated diseases. superantigens are potent activators of cd4+ t cells, causing rapid and massive proliferation of cells and cytokine production. this characteristic of superantigens can be exploited in diseases where strong immunologic responses are required, such as in the b16f10 animal model of melanoma. superantigen administration is able to significantly enhance ineffective anti-tumor immune responses, resulting in potent ... | 2001 | 11361034 |
| mammary gland involution is delayed by activated akt in transgenic mice. | activation of the antiapoptotic protein kinase akt is induced by a number of growth factors that regulate mammary gland development. akt is expressed during mammary gland development, and expression decreases at the onset of involution. to address akt actions in mammary gland development, transgenic mice were generated expressing constitutively active akt in the mammary gland under the control of the mouse mammary tumor virus (mmtv) promoter. analysis of mammary glands from these mice reveals a ... | 2001 | 11376107 |
| hormone-induced nucleosome positioning in the mmtv promoter is reversible. | the mouse mammary tumor virus (mmtv) promoter is induced by glucocorticoid hormone via the glucocorticoid receptor (gr). the hormone-triggered effects on mmtv transcription and chromatin structure were studied in xenopus oocytes. we previously showed that the nucleosomes organizing the mmtv promoter became translationally positioned upon hormone induction. a single gr-binding site was necessary and sufficient for the chromatin events to occur, while transcription and basal promoter elements were ... | 2001 | 11387213 |
| detection of viral superantigen-class ii mhc interactions at the cell surface. | mouse mammary tumor virus superantigens (vsags) must bind to class ii mhc proteins to activate t cells. although direct interaction of vsags with class ii proteins has been demonstrated biochemically, the details of this interaction are largely unresolved. to facilitate the study of class ii-vsag interactions, a sensitive assay has been developed that can detect binding of vsags to class ii proteins on the cell surface. the assay measures changes in vsag surface expression upon enzymatic removal ... | 2000 | 11395137 |
| pairing of vbeta6 with certain valpha2 family members prevents t cell deletion by mtv-7 superantigen. | superantigens (sag) are proteins of bacterial or viral origin able to activate t cells by forming a trimolecular complex with both mhc class ii molecules and the t cell receptor (tcr), leading to clonal deletion of reactive t cells in the thymus. sag interact with the tcr through the beta chain variable region (vbeta), but the tcr alpha chain has been shown to have an influence on the t cell reactivity. we have investigated here the role of the tcr alpha chain in the modulation of t cell reactiv ... | 2000 | 11395139 |
| prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by dna vaccination. | the her-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. the oncogenic potential of her-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. to test the efficacy of immune-based strategies in eliciting an antitumor response, we used the n#202 transgenic mouse model engineered to overexpress t ... | 2001 | 11402305 |
| reducing mammary cancer risk through premature stem cell senescence. | the reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. in a study of fvb/n mice with the transgene, wap-tgfbeta1, we discovered that mammary epithelial stem cells were prematurely aged due to ectopic expression of tgf-beta1. to test whether premature aging of mammary epithelial stem cells would have an impact on susceptibility or resistance to mammary cancer, female littermates from fvb/n x wap-tgf-beta1 mating ... | 2001 | 11402321 |
| transactivation of murine cyclin a by polyomavirus large and small t antigens. | polyomavirus large and small t antigens cooperate in the induction of s phase in serum-deprived swiss 3t3 cells. while the large t antigen is able to induce s phase-specific enzymes, we have recently shown that both t antigens contribute to the production of the cyclins e and a and that the small t antigen is essential for the induction of cyclin a-dependent cdk2 activity (s. schüchner and e. wintersberger, j. virol. 73:9266-9273, 1999). here we present our attempts to elucidate the mechanisms b ... | 2001 | 11413317 |
| molecular cloning and characterization of wnt3a and wnt14 clustered in human chromosome 1q42 region. | human wnt3a and wnt14 cdnas were cloned and characterized. wnt3a and wnt14 encoded wnt family protein of 352 and 365 amino acids, respectively. the 3.0-kb wnt3a mrna was moderately expressed in placenta, and the 4.4-kb wnt14 mrna was moderately expressed in skeletal muscle and heart. although wnt3a mrna was not detected in 35 human cancer cell lines, wnt14 mrna was expressed in gastric cancer cell lines tmk1, mkn7, mkn45 and kato-iii. wnt3a and wnt14 genes, clustered in the head to head manner w ... | 2001 | 11414706 |
| cooperating oncogenic events in murine mammary tumorigenesis: assessment of erbb2, mutant p53, and mouse mammary tumor virus. | we are investigating cooperating genetic events in the genesis of breast cancer, using the mouse as a model system. we have shown cooperativity between a mutant allele of p53 (p53-172h) and overexpressed erbb2 in mammary tumorigenesis in transgenic mice. we are now performing additional crosses to further examine oncogene cooperativity with erbb2 and p53-172h. we attempted to test the dominant oncogenic potential of p53-172h in an in vivo setting by crossing the p53-172h transgene together with ... | 2001 | 11417997 |
| glucocorticoid receptor-mediated chromatin remodeling in vivo. | the compaction of dna into chromatin provides an additional level of gene regulation in eukaryotes that may not be available to prokaryotes. when packaged as chromatin, most promoters are transcriptionally repressed, and transcription factors have reduced access to their binding sites. the glucocorticoid receptor (gr) is a ligand-activated transcription factor that regulates the activity of genes involved in many physiological processes. to regulate eukaryotic genes, the gr binds to target sites ... | 2001 | 11420719 |
| characterization of mouse mammary tumour virus-induced migration of lymphoid cells into lymph nodes. | we previously found that mtv-2+ lymph nodes (ln) implanted into mtv-2- mice underwent marked hyperplasia owing to the influx of lymphocytes. ln grafts infected with exogenous mouse mammary tumour viruses (mmtv), mmtv(fm) transmitted by fm mice and mmtv-2 produced by mtv-2, also swelled in mmtv-free recipients. mtv-3 and mtv-7 also displayed this capability. mtv-2-induced ln hyperplasia was earlier in onset and greater in extent when major histocompatibility complex (mhc) class ii i-e was express ... | 2001 | 11422903 |
| weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: an exploratory study in tumor-bearing mice. | at least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. we hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. | 2001 | 11423703 |
| protein kinase ck2 in mammary gland tumorigenesis. | protein kinase ck2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. recently, we have demonstrated that ck2 potentiates wnt/beta-catenin signaling in mammary epithelial cells. to determine whether ck2 overexpression contributes to mammary tumorigenesis, we have performed comparative studies of human and rat breast cancer specimens and we have engineered transgenic mice with dysregulated exp ... | 2001 | 11423974 |
| specific protection against breast cancers by cyclin d1 ablation. | breast cancer is the most common malignancy among women. most of these cancers overexpress cyclin d1, a component of the core cell-cycle machinery. we previously generated mice lacking cyclin d1 using gene targeting. here we report that these cyclin d1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. however, animals lacking cyclin d1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or wnt-1. our analy ... | 2001 | 11429595 |
| interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving stat5 (signal transducer and activator of transcription 5) but not ap-1. | cytokines and glucocorticoids (gcs) signaling pathways interfere with each other in the regulation of apoptosis and gene expression in the immune system. interleukin-2 (il-2), through the janus kinase/signal transducers and activators of transcription (jak/stat) and mitogen-activated protein kinase (mapk) pathways, activates stat5 and activated protein-1 (ap-1) transcription factors, respectively, which are known to repress glucocorticoid receptor (gr) activity, at least in part, through protein ... | 2001 | 11435608 |
| steroid hormone receptor-mediated histone deacetylation and transcription at the mouse mammary tumor virus promoter. | acetylation of lysines in histones h3 and h4 n-terminal tails is associated with transcriptional activation and deacetylation with repression. our studies with the mouse mammary tumor virus (mmtv) promoter in chromatin show significant levels of acetylation at promoter proximal and distal regions prior to transactivation. upon activation with glucocorticoids or progestins, promoter proximal histones become deacetylated within the region of inducible nuclease hypersensitivity. the deacetylation l ... | 2001 | 11448945 |
| large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter. | we have examined the relationship between transcription and chromatin structure using a tandem array of the mouse mammary tumor virus (mmtv) promoter driving a ras reporter. the array was visualized as a distinctive fluorescent structure in live cells stably transformed with a green fluorescent protein (gfp)-tagged glucocorticoid receptor (gr), which localizes to the repeated mmtv elements after steroid hormone treatment. also found at the array by immunofluorescence were two different steroid r ... | 2001 | 11448988 |
| [an antigen related to the mouse mammary cancer virus env gene product, detected in human lymphocytes, is associated with human breast cancer]. | expression of dna sequences homologous to sequences of env gene of mouse mammary tumor virus (mmtv) in the lymphocytes of patients with breast cancer and in subjects at a high risk of breast cancer has been reported. antigen analogous to envelope protein gp52, product of mmtv env gene, is detected in t lymphocytes of virtually all patients with breast cancer and extremely rarely in t cells of controls, where its expression is confined to b cells. for explaining such unexpected results, we studie ... | 2001 | 11449801 |
| identification and characterization of metal ion binding sites in rna. | | 2001 | 11460561 |
| identification of key amino acids of the mouse mammary tumor virus superantigen involved in the specific interaction with t-cell receptor v(beta) domains. | mouse mammary tumor virus (mmtv) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class ii by the variable region of the beta chain (v(beta)) of the t-cell receptor. the c-terminal 30 to 40 amino acids of the superantigen of different mmtvs display high sequence variability that correlates with the recognition of particular t-cell receptor v(beta) chains. interestingly, mmtv(sim) and mtv-8 superantigens are highly homologous but have ... | 2001 | 11462017 |
| histone h1 phosphorylation by cdk2 selectively modulates mouse mammary tumor virus transcription through chromatin remodeling. | transcriptional activation of the mouse mammary tumor virus (mmtv) promoter by ligand-bound glucocorticoid receptor (gr) is transient. previously, we demonstrated that prolonged hormone exposure results in displacement of the transcription factor nuclear factor 1 (nf1) and the basal transcription complex from the promoter, the dephosphorylation of histone h1, and the establishment of a repressive chromatin structure. we have explored the mechanistic link between histone h1 dephosphorylation and ... | 2001 | 11463824 |
| notch signaling in mammary gland tumorigenesis. | the notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. recent studies suggest that, depending on the cellular and developmental context, notch signaling may also affect cell proliferation and programmed cell death. mammals have four related notch genes. one of these, designated notch-4, was found to be a common integration site for the mouse mammary tumor virus in mouse mamm ... | 2001 | 11467450 |
| hormone-mediated dephosphorylation of specific histone h1 isoforms. | we have previously shown a connection between histone h1 phosphorylation and the transcriptional competence of the hormone inducible mouse mammary tumor virus (mmtv) promoter. prolonged exposure of mouse cells to dexamethasone concurrently dephosphorylated histone h1 and rendered the mmtv promoter refractory to hormonal stimulation and, therefore, transcriptionally unresponsive. using electrospray mass spectrometry, we demonstrate here that prolonged dexamethasone treatment differentially effect ... | 2001 | 11479299 |