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msx homeobox genes inhibit differentiation through upregulation of cyclin d1.during development, patterning and morphogenesis of tissues are intimately coordinated through control of cellular proliferation and differentiation. we describe a mechanism by which vertebrate msx homeobox genes inhibit cellular differentiation by regulation of the cell cycle. we show that misexpression of msx1 via retroviral gene transfer inhibits differentiation of multiple mesenchymal and epithelial progenitor cell types in culture. this activity of msx1 is associated with its ability to upr ...200111493556
targeted integration of foreign dna into a defined locus on chromosome 19 in k562 cells using aav-derived components.targeted integration of foreign dna is ideal for gene therapy, particularly when target cells such as hematopoietic cells actively divide and proliferate. adeno-associated virus (aav) has been shown to integrate its genome into a defined locus, aavs1 (19q13.3-qter). the inverted terminal repeat (itr) and rep proteins are responsible for this site-specific integration, and a system has been developed that delivers a gene preferentially into aavs1 by using these components of aav. we examined whet ...200111503961
some aspects of the morphology of the bittner virus. 197011515042
a virus (rmtdv) derived from chemically induced rat mammary tumors. i. isolation and general characteristics. 197011515058
bioactivity and virions in the blood of mice with mammary tumor virus. 197011515064
androgen responsiveness of the pituitary gonadotrope cell line lbetat2.androgens have a profound effect on the hypothalamic-pituitary axis by reducing the synthesis and release of the pituitary gonadotropin lh. the effect on lh is partly a consequence of a direct, steroid-dependent action on pituitary function. although androgen action has been well studied in vivo, in vitro cell models of androgen action on pituitary gonadotropes have been scarce. recently, an lh-expressing cell line, lbetat2, was generated by tumorigenesis targeted to the lh-producing cells of th ...200111524240
differential migration of in vivo primed b and t lymphocytes to lymphoid and non-lymphoid organs.our study describes tissue-specific migration of t and b cells during a localized anti-viral immune response. after mouse mammary tumor virus (mmtv) injection, b lymphocytes of the draining lymph node become infected and present a retroviral superantigen to cd4(+) t lymphocytes. infected b cells receive superantigen-mediated help in a fashion comparable to classical immune responses. to investigate the fate of t and b lymphocytes that had interacted via cognate help in the same peripheral lymph ...200111536158
glucocorticoid-regulated expression of exogenous human growth hormone gene in rats.the aim of this study was to control in vitro and in vivo expression of the growth hormone (gh) gene using a glucocorticoid-sensitive promoter, the mouse mammary tumor virus long terminal repeat (mmtv ltr). we inserted the cdna encoding the 20-kda form of human gh (20k-gh) downstream of the mmtv ltr of plasmid pmsg, and used lipofection to transfer it to 3y1 cells together with plasmid pmx, which contains a puromycin-resistant element. the secretion of gh from the selected transformants was dose ...200111545618
progesterone receptor isoform a inhibits isoform b-mediated transactivation in human amnion.human amnion cells were transfected with progesterone receptor a and/or b, and the progesterone-dependent reporter construct, mouse mammary tumor virus promoter (mmtv), linked to a luciferase gene. in progesterone receptor b-expressing amnion that had been cultured before the onset of labour, treatment with progesterone resulted in an eightfold increase of the reporter activity, whereas in laboured cells, no such increase was seen. in contrast, progesterone receptor a was a weak activator of tra ...200111553358
analyzing the contributions of chromatin structure in nuclear hormone receptor activated transcription in vivo.the authors have described three approaches for analyzing the chromatin architecture of a steroid-responsive promoter. mnase allows one to map the positions of nucleosomes on the target gene. the more sensitive restriction enzyme hypersensitivity procedure permits detection of changes in chromatin architecture upon hormonal stimulation. additional insight into transcriptional regulation of a gene can be obtained by using the related exoiii footprinting protocol, which provides complementary data ...200111554329
in vitro analysis of transcriptional repression of the mouse mammary tumor virus promoter.transcription of the proviral dna of mouse mammary tumor virus (mmtv) is induced by several classes of hormone-activated steroid receptor proteins. basal promoter activity in the absence of receptor-mediated activation is selectively repressed by a distal negative regulatory element (dnre) centered approximately 400 bp upstream of the transcription initiation site. an in vitro transcription system based on synthetic t-free cassette templates was developed to assess mmtv promoter activity, and dn ...200111554742
sequence and genetic analyses of the 3' terminus and integration sites of the riii/sa mouse mammary tumor (mmtv) exogenous provirus.the riii/sa mouse mammary tumor virus (mmtv) is one of several exogenous mmtv viruses transmitted to suckling mice through the milk. we report herein the nucleotide sequence of the exogenous riii/sa provirus from the central eco ri site through to the end of the u5 region encoded by the 3' ltr. we also provide a detailed sequence analysis often different 3' terminal exogenous mmtv proviral integration sites within mammary tumor dna obtained by the technique of genome walking. using a combination ...200111556399
differential interactions of specific nuclear factor i isoforms with the glucocorticoid receptor and stat5 in the cooperative regulation of wap gene transcription.the distal region (-830 to -720 bp) of the rat whey acidic protein (wap) gene contains a composite response element (core), which has been demonstrated previously to confer mammary gland-specific and hormonally regulated wap gene expression. point mutations in the binding sites for specific transcription factors present within this core have demonstrated the importance of both nuclear factor i (nfi) and stat5 as well as cooperative interactions with the glucocorticoid receptor (gr) in the regula ...200111564870
analysis of glucocorticoid and androgen receptor gene fusions delineates domains required for transcriptional specificity.androgen receptor (ar) and glucocorticoid receptor (gr) influence distinct physiologic responses in steroid-responsive cells despite their shared ability to selectively bind in vitro to the same canonical dna sequence (tgttct). while the dna-binding domains (dbds) of these receptors are highly conserved, the amino n-terminal domain (ntd) and hormone-binding domain (hbd) are evolutionarily divergent. to determine the relative contribution of these functional domains to steroid-specific effects in ...200111572317
mmtv promoter hypomethylation is linked to spontaneous and mnu associated c-neu expression and mammary carcinogenesis in mmtv c-neu transgenic mice.the erbb family of receptor tyrosine kinases is frequently implicated in neoplasia. amplification and overexpression of erbb2/neu has been found in 20 to 40% of human breast cancers. previous studies using mmtv/c-neu transgenic mice have linked rat neu overexpression to mammary tumor development. in this study, we provide evidence that rat neu overexpression in mammary tumors of mmtv/c-neu transgenic mice is always associated with demethylation of the mmtv promoter, whereas the normal mammary gl ...200111593408
molecular cloning and characterization of human wnt3.mouse wnt-3 is a proto-oncogene, which is activated by mouse mammary tumor virus (mmtv). human wnt3 cdna fragment, previously isolated by another group, corresponds to a partial coding sequence. wnt3 cdna, spanning the complete coding sequence, was isolated in this study. wnt3 encoded 355-amino-acid polypeptide with the n-terminal signal peptide and two n-linked glycosylation sites. wnt3 was most homologous to wnt3a (84.2% total amino-acid identity) among human wnts. the wnt3 gene on the human c ...200111604997
zinc-metallothionein levels are correlated with enhanced glucocorticoid responsiveness in mouse cells exposed to zncl(2), hgcl(2), and heat shock.metallothioneins (mts) are the major low molecular weight, zinc-binding proteins in mammalian cells. it has been hypothesized that they play a role in the function of zinc-dependent signal transduction proteins and transcription factors. we investigated the capacity of zinc and other metal ions and conditions to increase both zn-associated mt levels and the receptiveness of cells to transcriptional activation mediated by the zinc-dependent glucocorticoid receptor (gr). we studied, in a gr-respon ...200111606802
maspin expression inversely correlates with breast tumor progression in mmtv/tgf-alpha transgenic mouse model.maspin is a novel serine protease inhibitor (serpin) with tumor suppressive activity. to date, despite the mounting evidence implicating the potential diagnostic/prognostic and therapeutic value of maspin in breast and prostate carcinoma, the lack of a suitable animal model hampers the in vivo investigation on the role of maspin at different stages of tumor progression. in this study, we used mmtv/tgf-alpha transgenic mouse model to study the expression profile of maspin in mammary tumor progres ...200111641778
sleeping with the enemy--endogenous superantigens in humans.we usually think of superantigens (sag) as dangerous toxins that may cause toxic shock syndrome and death. now, based on two papers in this issue of immunity, it seems that we all have sag genes within us, lying dormant and waiting to be activated under special circumstances.200111672533
interleukin-4 up-regulates mouse mammary tumor virus expression yet is not required for in vivo virus spread.the mouse mammary tumor virus (mmtv) superantigen induces t-cell production of cytokines, such as interleukin-4, which in turn increase mmtv transcription. however, interleukin-4 is not required for in vivo virus spread, because mice lacking interleukin-4 or the stat6 transcription factor showed wild-type infection of lymphoid and mammary tissue. in spite of this, mammary tumor incidence was decreased in stat6 null mice.200111689671
antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporters.1. previous data demonstrate that the tricyclic antidepressant, desipramine, induces glucocorticoid receptor (gr) translocation from the cytoplasm to the nucleus in l929 cells and increases dexamethasone-induced gr-mediated gene transcription in l929 cells stably transfected with the mouse mammary tumour virus-chloramphenicol acetyltransferase (mmtv-cat) reporter gene (lmcat cells) (pariante et al., 1997). 2. to extend these findings, the present study has investigated the effects of 24 h coincu ...200111704655
nuclear receptor coactivator p160 proteins enhance the hiv-1 long terminal repeat promoter by bridging promoter-bound factors and the tat-p-tefb complex.we report that p160 nuclear receptor coactivators potentiate the transactivating activity of tat, the most potent virally encoded transactivator of hiv-1. one of the p160 proteins (grip1) is tethered to the hiv-1 long terminal repeat (ltr) through kappab-responsive elements, most likely via nf-kappab, with which it also associates through its coactivator motifs (lxxll motifs, "nr boxes"). indeed, the tat-stimulated kappab-defective hiv-1 ltr had a markedly impaired response to grip1, whereas nr ...200211704662
mammary epithelial-specific expression of the integrin-linked kinase (ilk) results in the induction of mammary gland hyperplasias and tumors in transgenic mice.the integrin linked kinase (ilk) is a cytoplasmic effector of integrin receptors, involved in the regulation of integrin binding properties as well as the activation of cell survival and proliferative pathways, including those involving map kinase, pkb/akt and gsk-3beta. overexpression of ilk in cultured intestinal and mammary epithelial cells has been previously shown to induce changes characteristic of oncogenic transformation, including anchorage-independent growth, invasiveness, suppression ...200111704830
functional mammary gland development and oncogene-induced tumor formation are not affected by the absence of the retinoblastoma gene.loss of cell cycle regulation in mammary epithelium results in impaired mammary gland development and neoplasia. we investigated the consequences of the absence of prb in mammary epithelial cells during normal development and in mice that express an oncogene in the mammary epithelium. since prb-deficiency results in embryonic lethality, we transplanted prb-null mammary anlagen into wild hosts. prb-deficient mammary epithelia were capable of functional differentiation in term animals and they reg ...200111704837
in vivo analysis of mammary and non-mammary tumorigenesis in mmtv-cyclin d1 transgenic mice deficient in p53.overexpression of the cyclin d1 oncogene and inactivation of the p53 tumor suppressor have both been implicated in substantial proportions of sporadic human breast cancers. transgenic mice with cyclin d1 overexpression targeted to mammary tissue by the mmtv enhancer-promoter have been shown to develop mammary cancers. to investigate the relationship between pathways driven by cyclin d1 overexpression and p53 loss during the development of breast cancers, we crossed mmtv-cyclin d1 mice with p53 h ...200111708657
up-regulation by clarithromycin of alpha(1)-acid glycoprotein expression in liver and primary cultured hepatocytes.alpha(1)-acid glycoprotein (agp) is the major transport protein for cationic drugs, endogenous ligands, and some anionic drugs in plasma. hepatic synthesis and secretion of agp are altered during acute inflammation as well as by a number of drugs. this alteration could influence the binding of drugs and its biological function. macrolide antibiotics are widely used in the treatment of a variety of infectious diseases. the effects of macrolide antibiotics have been studied with respect to rat agp ...200111709199
tissue-specific androgen responses in primary cultures of lacrimal epithelial cells studied by adenoviral gene transfer.the lacrimal gland secretes most of the water and many proteins present in tear fluid. the composition of the tear fluid is affected dramatically by androgens, an observation which has been linked to the fact that more than 90% of the patients with sjögren syndrome are female. although the presence of androgen receptors in the lacrimal gland has been established, the molecular biology of the protective effects of androgens remains largely unknown. here, we report the use of primary cultures of t ...200111717002
the pea3 subfamily ets genes are required for her2/neu-mediated mammary oncogenesis.the pea3 ets transcription factor is overexpressed in the vast majority of human breast tumors and in nearly all of those of the her2/neu-positive subclass. pea3 is also overexpressed in various transgenic mouse models of this disease. whether pea3 plays an essential role in her2/neu-mediated oncogenesis has heretofore not been addressed.200111719215
transgenic polyoma middle-t mice model premalignant mammary disease.mice transgenic for the polyomavirus middle t (pyv-mt) gene have been widely used to study mammary tumorigenesis and metastasis. although numerous molecular insights were gained from the analysis of these transgenic malignant tumors, the early events leading to malignant transformation have not been systematically investigated nor has the biological potential of hyperplastic lesions been documented. this paper presents the first comprehensive histopathological characterization of transgenic pyv- ...200111719463
natural cd4+ cd25+ regulatory t cells. their role in the control of superantigen responses.cd4 regulatory t cells have a major role in controlling the immune response to self and foreign antigens. natural cd4+ cd25+ t cells are a major component of the regulatory subset. their absence is associated with the development of autoimmune and inflammatory diseases and with abnormal peripheral t-cell homeostasis. two main characteristics discriminate natural cd4+ cd25+ t cells from their cd4+ cd25- counterparts, namely their cytokine production profile and their behavior during tolerance ind ...200111722633
conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation.in the mammary gland bcl-x is the most abundant cell survival factor from the bcl-2 family. since bcl-x null mice die around day 12 of embryogenesis, the relevance of this protein in organ development and function is poorly understood. in erythroid cells bcl-x gene expression is controlled by cytokines and the transcription factor stat5 (signal transducer and activator of transcription). however, we identified that bcl-x rna levels in mammary tissue from prolactin receptor- and stat5-null mice w ...200111731240
accurate chromatin organization of the mouse mammary tumor virus promoter determines the nature of the synergism between transcription factors.the mechanism underlying the synergism between transcription factors in eukaryotic gene expression is not fully understood. in minichromosomes assembled in vitro the synergism between steroid hormone receptors (shrs) and nuclear factor 1 (nf1) on the mouse mammary tumor virus (mmtv) promoter does not require the proline-rich transactivation domain (prd) of nf1. here we show that similar results are obtained in yeast. in contrast, replacing the native hormone-responsive elements (hres) by a singl ...200211733499
ku represses the hiv-1 transcription: identification of a putative ku binding site homologous to the mouse mammary tumor virus nre1 sequence in the hiv-1 long terminal repeat.ku has been implicated in nuclear processes, including dna break repair, transcription, v(d)j recombination, and telomere maintenance. its mode of action involves two distinct mechanisms: one in which a nonspecific binding occurs to dna ends and a second that involves a specific binding to negative regulatory elements involved in transcription repression. such elements were identified in mouse mammary tumor virus and human t cell leukemia virus retroviruses. the purpose of this study was to inve ...200211733502
wnt signaling in breast cancer: have we come full circle?since the original identification of wnt1 as a mammary oncogene in mouse mammary tumor virus infected mice, questions have been asked about its relevance to human breast cancer. wnt1 is now known to be one of a large family of wnt genes encoding structurally similar secreted signaling proteins, several of which are functionally redundant. the principal intracellular signaling pathway activated by these proteins has been elucidated in recent years. components of this pathway include proto-oncogen ...200111737884
pten deficiency: a role in mammary carcinogenesis.the pten gene is often mutated in primary human tumors and cell lines, but the low rate of somatic pten mutation in human breast cancer has led to debate over the role of this tumor suppressor in this disease. the involvement of pten in human mammary oncogenesis has been implicated from studies showing that germline pten mutation in cowden disease predisposes to breast cancer, the frequent loss of heterozygosity at the pten locus, and reduced pten protein levels in sporadic breast cancers. to as ...200111737885
expression of the androgen-dependent mmtv-specific orf gene in shionogi 115 mouse mammary tumor cells.the shionogi 115 (s115) mouse mammary tumor cells express the mmtv-specific 1.7 kb mrna (orf) at a high level in the presence of androgens. in lymphoid cells the orf-gene encodes a superantigen which has an important role in establishing self-tolerance but in mammary and breast cancer cells the function of the orf gene is unclear. in the present work we studied the expression of the s115 mammary tumor cell orf sequence and its role in the androgen regulated growth of s115 cells. the cloning and ...200111738549
impaired mammary gland and lymphoid development caused by inducible expression of axin in transgenic mice.axin is a component of the canonical wnt pathway that negatively regulates signal transduction by promoting degradation of beta-catenin. to study the role of axin in development, we developed strains of transgenic mice in which its expression can be manipulated by the administration of doxycycline (dox). animals carrying both mouse mammary tumor virus (mmtv)-reverse tetracycline transactivator and tetracycline response element (tre)2-axin-green fluorescent protein (gfp) transgenes exhibited dox- ...200111739413
hormone-dependent, carm1-directed, arginine-specific methylation of histone h3 on a steroid-regulated promoter.activation of gene transcription involves chromatin remodeling by coactivator proteins that are recruited by dna-bound transcription factors. local modification of chromatin structure at specific gene promoters by atp-dependent processes and by posttranslational modifications of histone n-terminal tails provides access to rna polymerase ii and its accompanying transcription initiation complex. while the roles of lysine acetylation, serine phosphorylation, and lysine methylation of histones in ch ...200111747826
regulation of cyclin d1 and p16(ink4a) is critical for growth arrest during mammary involution.a coordinated growth arrest during mammary involution completes the dramatic changes in mammary cell proliferation seen during pregnancy and lactation. signals regulating this arrest are poorly understood, despite their potential relevance to oncogenesis. here we report that the arrest involves a unique pulse of p16(ink4a) expression in vivo, which accompanies decreased cyclin d1 expression and a shift to an active repressor e2f4 complex. we used ink4a/arf-/- mice as well as cyclin d1 and p16(in ...200111751403
direct interaction of the krüppel-like family (klf) member, bteb1, and pr mediates progesterone-responsive gene expression in endometrial epithelial cells.the present study was undertaken to evaluate the underlying mechanism(s) by which pr and a krüppel-like family member, basic transcription element binding protein (bteb1), mediate endometrial epithelial expression of pregnancy-associated genes. human endometrial carcinoma cell lines (hec-1-a) expressing high and low levels of bteb1 were transiently transfected with a human pr isoform (pr-b) expression construct and a luciferase reporter gene driven by the uteroferrin gene promoter that is respon ...200211751593
functional association of pr and ccaat/enhancer-binding protein beta isoforms: promoter-dependent cooperation between pr-b and liver-enriched inhibitory protein, or liver-enriched activatory protein and pr-a in human endometrial stromal cells.activation of the decidual prl (dprl) promoter, a major differentiation marker in human endometrial stromal (es) cells, by camp is effected through the induction and binding of ccaat/enhancer-binding protein-beta (c/ebpbeta) to two overlapping cognate response elements in the promoter region dprl-332/-270. progesterone is essential for decidualization and potently enhances camp-dependent dprl promoter activity. we now demonstrate that both liganded pr isoforms, pr-a and pr-b, are capable of tran ...200211773445
activation of beta -catenin signaling in differentiated mammary secretory cells induces transdifferentiation into epidermis and squamous metaplasias.mammary anlagen are formed in the embryo as a derivative of the epidermis, a process that is controlled by lef-1 and therefore possibly by beta-catenin. to investigate the role of beta-catenin signaling in mammary alveolar epithelium, we have stabilized endogenous beta-catenin in differentiating alveolar epithelium through the deletion of exon 3 (amino acids 5-80) of the beta-catenin gene. this task was accomplished in mice carrying a floxed beta-catenin gene and a cre transgene under control of ...200211773619
activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma.the retinoblastoma (rb) tumor suppressor controls cellular proliferation, survival, and differentiation and is functionally inactivated by mutations or hyperphosphorylation in most human cancers. although activation of endogenous rb is thought to provide an effective approach to suppress cell proliferation, long-term inhibition of apoptosis by active rb may have detrimental consequences in vivo. to directly test these paradigms, we targeted phosphorylation-resistant constitutively active rb alle ...200211777937
induction of germinal centers by mmtv encoded superantigen on b cells.it has not been established whether an endogenous superantigen (sag) expressed on b cells can induce germinal centers (gcs). an interesting model is that of mammary tumor virus encoded viral sags, which induce vigorous t cell proliferation and are predominantly expressed on activated b cells. we have used this model to analyze the possibility that direct stimulation of mtv7+ dba/2 b cells by vsag-responsive (vbeta6+) balb/c t cells can give rise to gcs. injection of balb/c scid mice i.v. with 2 ...200111785670
in vitro response of v-ha-ras transgenic mouse lymphocytes after in vivo treatment with alcohol.oncomouse is a transgenic mouse carrying an activated v-ha-ras oncogene under the control of the mouse mammary tumor virus promoter. the objective of this paper was to learn if the in vitro secretion of il-2 and ifn-gamma and the release of sil-2r by oncomice splenocytes and thymocytes depended on the presence of the oncogene product, on the in vivo pretreatment with alcohol, or on the in vitro treatment with cocaine or morphine. oncomice thymocytes released less sil-2r than fvb thymocytes. alco ...200111792018
in vitro response of v-ha-ras transgenic mouse lymphocytes after in vivo treatment with cocaine.oncomouse is a transgenic mouse carrying an activated v-ha-ras oncogene under the control of the mouse mammary tumor virus promoter. the objective of this paper was to learn if the in vitro secretion of il-2 and ifn-gamma and the release of sil-2r by oncomice spleen and thymus cells depended on the presence of the oncogene product, on the in vivo pretreatment with cocaine, or on the in vitro treatment with cocaine or morphine. oncomice thymocytes from different experimental groups released less ...200111792019
androgen induction of in vitro prostate cell differentiation.to better understand androgen action in normal prostate cells, we characterized the androgen growth response of an immortalized nontumorigenic rat prostate cell line called ca25 that had been stably transfected with androgen receptor (ar) cdna. surprisingly, we found that ar(+) ca25 cells grew slower in the presence of dihydrotestosterone (dht), whereas the growth of ar(-) ca25 cells was not affected by the hormone. dht-mediated growth inhibition of ca25 cells was not attributable to an increase ...200211801526
delayed mammary gland involution in mmtv-akt1 transgenic mice.akt1/protein kinase balpha is a protein-serine/threonine kinase that regulates multiple targets involved in cell survival and cell cycle progression in a variety of cell types including breast cancer cells. to explore the role of akt1 in mammary gland function and tumorigenesis, transgenic mice were generated that express human akt1 under the control of the mmtv promoter. virgin transgenic mice did not exhibit a dominant phenotype, but upon cessation of lactation, a notable delay in involution o ...200211803463
anticarcinogenic effects of isoflavones may be mediated by genistein in mouse mammary tumor virus-induced breast cancer.isoflavones are known to exert anticancer effects. these effects were examined using two isoflavones, biochanin a and daidzein, in a mouse mammary tumor virus (mmtv)-induced spontaneous breast cancer model. emphasis was placed on isoflavone metabolism by the intestinal microflora and changes in estrogen levels. germ-free (gf) mice and their conventionalized (cv) counterparts were assigned to three diet groups: (1) control diet, (2) biochanin a and (3) daidzein. in all groups, urine was collected ...200211810047
spatial and temporal expression of the cre gene under the control of the mmtv-ltr in different lines of transgenic mice.cre-loxp based gene deletion approaches hold great promise to enhance our understanding of molecular pathways controlling mammary development and breast cancer. we reported earlier the generation of transgenic mice that express the cre recombinase under the control of the mouse mammary tumor virus (mmtv) long terminal repeat (ltr). these mice have become a valuable research tool to delete genes specifically in the mammary gland, other secretory organs, and the female germline. we have now charac ...200111817542
domain interactions between coregulator ara(70) and the androgen receptor (ar).the coregulator function of ar-associated protein 70 (ara(70)) was investigated to further characterize its interaction with the ar. using a yeast two-hybrid assay, androgen-dependent binding of ara(70) deletion mutants to the ar ligand-binding domain (lbd) was strongest with ara(70) amino acids 321-441 of the 614 amino acid ara(70) protein. mutations adjacent to or within an fxxlf motif in this 120-amino acid region abolished androgen-dependent binding to the ar-lbd both in yeast and in glutath ...200211818501
the histone deacetylase inhibitor trichostatin a blocks progesterone receptor-mediated transactivation of the mouse mammary tumor virus promoter in vivo.post-translational modifications of histones play an important role in modulating gene transcription within chromatin. we used the mouse mammary tumor virus (mmtv) promoter, which adopts an ordered nucleosomal structure, to investigate the impact of a specific inhibitor of histone deacetylase, trichostatin a (tsa), on progesterone receptor-activated transcription. tsa induced global histone hyperacetylation, and this effect occurred independently of the presence of hormone. interestingly, chroma ...200211821430
dramatic increase in lymph node dendritic cell number during infection by the mouse mammary tumor virus occurs by a cd62l-dependent blood-borne dc recruitment.despite the information dealing with the differential phenotype and function of the main mouse dendritic cell (dc) subpopulations, namely, cd8alpha(-) and cd8alpha(+) dcs, their origin and involvement in antiviral immune responses in vivo are still largely unknown. to address these issues, this study used the changes occurring in dc subpopulations during the experimental infection by the swiss (sw) strain of the mouse mammary tumor virus (mmtv). mmtv(sw) induced an 18-fold increase in lymph node ...200211830477
green tea polyphenol epigallocatechin-3 gallate inhibits her-2/neu signaling, proliferation, and transformed phenotype of breast cancer cells.overexpression of the epidermal growth factor receptor family member her-2/neu in breast cancer is associated with poor prognosis. with evidence accumulating for a chemopreventive role of green tea polyphenols, the effects of epigallocatechin-3 gallate (egcg) on her-2/neu-overexpressing breast cancer cells were examined. egcg inhibited mouse mammary tumor virus (mmtv)-her-2/neu nf639 cell growth in culture and soft agar. egcg reduced signaling via the phosphatidylinositol 3- kinase, akt kinase t ...200211830514
interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ mouse mammary tumor virus-induced mammary carcinomas.we examined the ability of recombinant murine interleukin-12 (rmil-12) to inhibit the vasculature and growth of mammary carcinomas arising in situ in mouse mammary tumor virus (mmtv)-infected female c3h/hen mice. although it is a potent antiangiogenic and antitumor agent in many transplanted murine tumor models, rmil-12 failed to inhibit the vascularity, reduce the perfusion, or alter the growth of these autochthonous carcinomas. factors intrinsic to these tumor cells were unlikely to be respons ...200211830529
failure of steroid regulation of the mmtv promoter in a small cell lung cancer cell line is caused by a dna sequence flanking the glucocorticoid response element.we have previously described a panel of human small cell lung carcinoma (sclc) cell lines that have profound glucocorticoid resistance, resulting from various molecular defects in glucocorticoid signalling. however, in one sclc cell line, corl103, the cause of the resistance is unknown. these cells are refractory to dexamethasone stimulation of mmtv even when exogenous wild-type glucocorticoid receptor (gr) is co-transfected. this is in contrast to cell lines dms79 and corl24 where resistance is ...200211834447
selection for c-myc integration sites in polyclonal t-cell lymphomas.type b leukemogenic virus (tblv) is highly related to mouse mammary tumor virus but induces rapidly appearing t-cell lymphomas in mice. unlike other t-cell tumors induced by retroviruses, only 5 to 10% of tblv-induced lymphomas have detectable viral integrations near c-myc by southern blotting, whereas northern blotting has shown that most tumors have two- to sixfold overexpression of c-myc rna. in this report, pcr was used to demonstrate that at least 30% of these lymphomas have tblv insertions ...200211836386
cdp binding to multiple sites in the mouse mammary tumor virus long terminal repeat suppresses basal and glucocorticoid-induced transcription.mouse mammary tumor virus (mmtv) is transcribed at high levels in the lactating mammary gland to ensure transmission of virus from the milk of infected female mice to susceptible offspring. we previously have shown that the transcription factor ccaat displacement protein (cdp) is expressed in high amounts in virgin mammary gland, yet dna-binding activity for the mmtv long terminal repeat (ltr) disappears as mammary tissue differentiates during lactation. cdp is a repressor of mmtv expression and ...200211836394
expression analysis of pediatric solid tumor cell lines using oligonucleotide microarrays.we identified patterns of differentially-expressed genes in cell lines derived from several pediatric solid tumors. affymetrix human cancer g110 arrays, carrying 1,700 cancer-associated genes, were applied to a panel of 11 cell lines originating from ewing tumors (ets), neuroblastomas, and malignant melanoma of soft parts. hierarchical clustering clearly differentiated these 3 entities and revealed groups of 75, 102, and 36 gene probe-sets exhibiting tumor-type specific up-regulation in these ce ...200211836553
human endogenous retrovirus iddmk(1,2)22 and mouse mammary tumor virus superantigens differ in their ability to stimulate murine t cell hybridomas.recently, a newly identified human herv-k18 like endogenous retrovirus (iddmk(1,2)22) has been associated to the etiology of type i diabetes (iddm). although the exact mechanism remains unclear, it was postulated that the 3' end orf product of the env gene of iddmk(1,2)22 would trigger a v beta 7-specific human t cell expansion leading to their infiltration in the pancreas of afflicted patients and to the autoimmune destruction of the insulin-producing beta cells. since then, such superantigen ( ...200211841850
murine retroviruses activate b cells via interaction with toll-like receptor 4.although most retroviruses require activated cells as their targets for infection, it is not known how this is achieved in vivo. a candidate protein for the activation of b cells by either mouse mammary tumor virus (mmtv) or murine leukemia virus is the toll-like receptor 4 (tlr4), a component of the innate immune system. mmtv caused b cell activation in c3h/hen mice but not in c3h/hej or balb/c (c.c3h tlr4(lps-d)) congenic mice, both of which have a mutant tlr4 gene. this activation was indepen ...200211854525
a novel cell line, mda-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists.the u.s. environmental protection agency has proposed that in vitro assays for estrogen receptor (er)- and androgen receptor (ar)-mediated actions be included in a tier-i screening battery to detect hormonally active chemicals. herein we describe the development of a novel stable cell line, mda-kb2, for screening of androgen agonist and antagonists and to characterize its specificity and sensitivity to endocrine-disrupting chemicals. the breast cancer cell line, mda-mb-453, was stably transforme ...200211861974
development of two androgen receptor assays using adenoviral transduction of mmtv-luc reporter and/or har for endocrine screening.the discovery of xenobiotics that interfere with androgen activity has highlighted the need to assess chemicals for their ability to modulate dihydrotestosterone (dht)-receptor binding. previous test systems have used cells transfected with plasmid containing a reporter gene. here we report the use of transduction for gene delivery and assessment of the modulation of dht-induced gene activation. transduction, the ability of replication-defective viruses to deliver biologically competent genes, i ...200211861975
vanadate increases glucocorticoid receptor-mediated gene expression: a novel mechanism for potentiation of a steroid receptor.transition metal oxyanions, such as molybdate, tungstate and vandadate, have been shown to prevent in vitro hormone-induced activation of the glucocorticoid receptor (gr) by blocking dissociation of the gr/heat shock protein heterocomplex. in this work, we report a novel effect of vanadate: in vivo potentiation of gr-mediated gene expression. in cells stably-transfected with complex (mouse mammary tumor virus (mmtv)) or minimal gr-regulated cat reporters, treatment with 500mum vanadate caused ca ...200211867262
genetic instability favoring transversions associated with erbb2-induced mammary tumorigenesis.it has been argued that genetic instability is required to generate the myriad mutations that fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility syndromes harbor defects in specific genes that normally maintain dna integrity. however, the vast majority of human cancers arise sporadically, in the absence of deficiencies in known "mutator" genes. we used a cii-based mutation detection assay to show that the mean frequency of forward mutations in prima ...200211867754
genetic engineering of the glucocorticoid receptor by fusion with the herpes viral protein vp22 causes selective loss of transactivation.the development of methods for engineering proteins with novel properties opens the way to manipulating intracellular processes in a therapeutically useful way. glucocorticoids, acting via glucocorticoid receptors (gr), are potent anti-inflammatory agents, acting to oppose nuclear factor kappa b (nf kappa b) function. the herpes viral protein, vp22, has been reported to confer intercellular trafficking activity on 'cargo' proteins, potentially facilitating gene therapy with intracellular protein ...200211874710
a novel doxycycline-inducible system for the transgenic analysis of mammary gland biology.normal developmental events such as puberty, pregnancy, and parity influence the susceptibility of the mammary gland to tumorigenesis in both humans and rodent model systems. unfortunately, constitutive transgenic mouse models that rely on mammary-specific promoters to control transgene expression have limited utility for studying the effect of developmental events on breast cancer risk since the hormonal signals governing these events also markedly influence transgene expression levels. a novel ...200211874978
characterization of a common precursor population for dendritic cells.dendritic cells (dcs) are essential for the establishment of immune responses against pathogens and tumour cells, and thus have great potential as tools for vaccination and cancer immunotherapy trials. experimental evidence has led to a dual dc differentiation model, which involves the existence of both myeloid- and lymphoid-derived dcs. but this concept has been challenged by recent reports demonstrating that both cd8- and cd8+ dcs, considered in mice as archetypes of myeloid and lymphoid dcs r ...200211875574
mode of inhibition of hiv-1 reverse transcriptase by polyacetylenetriol, a novel inhibitor of rna- and dna-directed dna polymerases.polyacetylenetriol (pat), a natural marine product from the mediterranean sea sponge petrosia sp., was found to be a novel general potent inhibitor of dna polymerases. it inhibits equally well the rna- and dna-dependent dna polymerase activities of retroviral reverse transcriptases (rts) (i.e. of hiv, murine leukaemia virus and mouse mammary tumour virus) as well as cellular dna polymerases (i.e. dna polymerases alpha and beta and escherichia coli polymerase i). a study of the mode and mechanism ...200211879196
a 320-kilobase artificial chromosome encoding the human hla dr3-dq2 mhc haplotype confers hla restriction in transgenic mice.mhc class ii haplotypes control the specificity of th immune responses and susceptibility to many autoimmune diseases. understanding the role of hla class ii haplotypes in immunity is hampered by the lack of animal models expressing these genes as authentic cis-haplotypes. in this study we describe transgenic expression of the autoimmune prone hla dr3-dq2 haplotype from a yeast artificial chromosome (yac) containing an intact similar320-kb region from hla dra to dqb2. in yac-transgenic mice hla ...200211884478
erbb2/neu-induced, cyclin d1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells.erbb2/neu destabilizes the cyclin-dependent kinase (cdk) inhibitor p27 and increases expression of cyclin d1. therefore, we studied the roles of p27 and cyclin d1 in erbb2-mediated mammary epithelial cell transformation. overexpression of erbb2 or cyclin d1 in p27(+/-) primary murine mammary epithelial cells resulted in increased proliferation, cyclin d1 nuclear localization, and colony formation in soft agar compared to those in p27(+/+) cells. in contrast, erbb2- or cyclin d1-overexpressing p2 ...200211884607
representational difference analysis in a lupus-prone mouse strain results in the identification of an unstable region of the genome on chromosome 11.bxsb mice develop a lupus-like autoimmune syndrome. we have previously identified several intervals that were linked to disease and, in an attempt to characterise lupus susceptibility genes within these intervals, we have sought to isolate differentially expressed genes. representational difference analysis was used to compare gene expression between bxsb and c57bl/10 mice using spleen and thymus as a source of mrna. the majority of differentially expressed sequences identified were immunoglobul ...200211884638
sequence and expression of the mouse mammary tumour virus env gene.we have determined the dna sequence of the envelope gene region of the gr strain of mouse mammary tumour virus. the sequence extends for 3012 nucleotides from the single ecori site to beyond the psti site in the 3' long terminal repeat (ltr) of the provirus. there is a major open reading frame from nucleotides 752 to 2818 which encompasses the entire env gene. this reading frame extends through a polypurine tract and into the ltr. there is another open reading frame from the first nucleotide to ...198311894899
malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eif3e).several components of translation, e.g. eif4e and pkr, are implicated in cancer. the e-subunit (p48) of mammalian initiation factor 3 is encoded by the int6 gene, a common site for integration of the mouse mammary tumor virus genome, leading to the production of a truncated eukaryotic initiation factor-3e (eif3e). stable expression of a truncated eif3e in nih 3t3 cells causes malignant transformation by four criteria: foci formation; anchorage independent growth; accelerated growth; and lack of ...200211904180
new tools for the construction of replication-competent adenoviral vectors with altered e1a regulation.we have designed new vectors for the construction of recombinant adenoviruses containing the early region 1a (e1a) gene under the transcriptional control of heterologous promoters. the normal e1a regulatory elements have been replaced by a convenient set of unique restriction enzyme sites, allowing for introduction of gene regulatory cassettes with relative ease. subsequent rescue generates recombinant conditionally replicating adenovirus in which the transcription of e1a is under alternative co ...200211906731
preferential infection of immature dendritic cells and b cells by mouse mammary tumor virus.until now it was thought that the retrovirus mouse mammary tumor virus preferentially infects b cells, which thereafter proliferate and differentiate due to superantigen-mediated t cell help. we describe in this study that dendritic cells are infectable at levels comparable to b cells in the first days after virus injection. moreover, igm knockout mice have chronically deleted superantigen-reactive t cells after mmtv injection, indicating that superantigen presentation by dendritic cells is suff ...200211907107
the viral transactivator e1a regulates the mouse mammary tumor virus promoter in an isoform- and chromatin-specific manner.proteins encoded by the adenovirus e1a gene regulate both cellular and viral genes to mediate effects on cell cycle, differentiation, and cell growth control. we have identified the mouse mammary tumor virus (mmtv) promoter as a target of e1a action and investigated the role nucleoprotein structure plays in its response to e1a. both 12 and 13 s forms target the mmtv promoter when it has a disorganized and accessible chromatin configuration. however, whereas the 13 s form is stimulatory, the 12 s ...200211909860
suppression of murine mammary carcinoma growth and metastasis by hsvtk/gcv gene therapy using in vivo electroporation.the effectiveness of electroporation as a means of gene transfection, both in vitro and in vivo, was tested using the herpes simplex virus 1 thymidine kinase (hsvtk) gene in combination with ganciclovir (gcv) administration as therapy against murine mammary cancer. approximately 80% of bjmc3879 metastatic mammary carcinoma cells, derived from mmtv-infected balb/c mice, died as a result of hsvtk/gcv treatment 72 hours after the transfection; decreased dna synthesis was also seen. mammary tumors i ...200211916241
mmtv-associated transcription factor binding sites increase nm23-h1 metastasis suppressor gene expression in human breast carcinoma cell lines.we hypothesize that elevation of nm23-hi metastasis suppressor gene expression in micrometastatic tumor cells may reduce their subsequent colonization and invasion, and induce differentiation, with a clinical benefit. this report presents the first analysis of the nm23-hi promoter to identify sites which can increase its transcription. deletion mapping of a 2.1 kb nm23-h1 promoter fragment tethered to a reporter gene identified three regions involved in its differential expression levels among a ...200211918081
neonatal infection with a milk-borne virus is independent of beta7 integrin- and l-selectin-expressing lymphocytes.mouse mammary tumor virus (mmtv) is acquired by neonates through milk and first infects lymphocytes in peyer's patches. we show here that newborn mice lacking beta7 integrin or l-selectin were infected with mmtv at wild-type levels in both their lymphoid and mammary tissues. superantigen-mediated activation and cognate t cell deletion were also unimpaired in both types of null mice. a large proportion of neonatal peyer's patch lymphocytes in wild-type mice were beta7 and beta1 integrin low and b ...200211920560
differential effects of p21(waf1/cip1) deficiency on mmtv-ras and mmtv-myc mammary tumor properties.p21(waf1/cip1) (p21) functions as a cyclin-dependent kinase (cdk) inhibitor and is a key mediator of p53-dependent growth arrest. however, its role in cell cycle regulation is complex, because it also appears to promote cdk activity in certain experimental contexts. its potential role in tumor suppression was evaluated in mmtv-ras and mmtv-myc transgenic mice that were interbred to p21(waf1/cip1) knockout mice (p21-/-). p21 deficiency had differential effects on tumor incidence and age of onset, ...200211929828
presence of mouse mammary tumor virus specifically alters the body odor of mice.it has long been recognized that various genetic and metabolic human disorders alter body odor, which is not surprising because they may alter body chemistry. thus, it has been suggested that some human diseases may be diagnosed by odor alone. in that regard, the mouse mammary tumor virus (mmtv) and its tumors of mice, which may have human counterparts, are of special interest because of the need for basic research possible only in inbred and genetically defined animals. accordingly, we now show ...200211929982
female pseudohermaphroditism caused by a novel homozygous missense mutation of the gr gene.familial glucocorticoid resistance is characterized by increased cortisol secretion without clinical evidence of hypercortisolism, but with manifestations of androgen and mineralocorticoid excess. this condition is mainly caused by mutations of the gr gene that cause inadequate transduction of the glucocorticoid signal in glucocorticoid target tissues. the clinical features of glucocorticoid resistance in females include hirsutism, acne, male pattern baldness, oligomenorrhea, and oligoanovulatio ...200211932321
erbb-beta-catenin complexes are associated with human infiltrating ductal breast and murine mammary tumor virus (mmtv)-wnt-1 and mmtv-c-neu transgenic carcinomas.simultaneous deregulation of both wnt and erbb growth factors has previously been shown to result in the cooperative induction of mammary gland tumors. using the murine mammary tumor virus (mmtv)-wnt-1 transgenic model of mammary carcinoma, we have identified an unvarying association between beta-catenin and epidermal growth factor receptor/c-neu (erbb1/erbb2) heterodimers in mammary gland tumors, indicating a requirement for erbb signaling in wnt-mediated tumorigenesis. expansion of these obser ...200211950845
perinatal blockade of b7-1 and b7-2 inhibits clonal deletion of highly pathogenic autoreactive t cells.a number of in vitro studies have suggested that costimulatory molecules b7-1 and b7-2 and their receptor cd28 can promote clonal deletion, and limited in vivo studies have indicated that cd28 is involved in the clonal deletion of some t cells. however, the significance of b7-mediated clonal deletion in preventing autoimmune diseases has not been studied systematically. here we report that the perinatal blockade of b7-1 and b7-2 substantially inhibits the clonal deletion of t cells in the thymus ...200211956287
identification of human homologues of the mouse mammary tumor virus receptor.human breast tumors contain dna sequences with high homology to the mouse mammary tumor virus (mmtv) env gene. env encodes the membrane glycoprotein that binds to the mmtv receptor (mtvr) in mouse tissues and is required for infection. if humans become infected with mmtv, identification of a human mtvr might shed light on the mechanism of infection. here, we identified two human genes, mtvr1 and mtvr2, encoding proteins highly related to the mouse receptor. mtvr-related sequences were also detec ...200211958456
proteasome inhibitors reduce luciferase and beta-galactosidase activity in tissue culture cells.reporter enzymes are commonly used in cell biology to study transcriptional activity of genes. recently, reporter enzymes in combination with compounds that inhibit proteasome function have been used to study the effect of blocking transcription factor degradation on gene activation. while investigating the effect of proteasome inhibition on steroid receptor activation of the mouse mammary tumor virus (mmtv) promoter, we found that treatment with proteasome inhibitors enhanced glucocorticoid act ...200211959849
viral late domains. 200211967285
atp-dependent mobilization of the glucocorticoid receptor during chromatin remodeling.chromatin remodeling by the glucocorticoid receptor (gr) is associated with activation of transcription at the mouse mammary tumor virus (mmtv) promoter. we reconstituted this nucleoprotein transition with chromatin assembled on mmtv dna. the remodeling event was atp dependent and required either a nuclear extract from hela cells or purified human swi/snf. through the use of a direct interaction assay (magnetic bead pull-down), we demonstrated recruitment of human swi/snf to mmtv chromatin by gr ...200211971959
testing mouse mammary tumor virus superantigen as adjuvant in cytotoxic t-lymphocyte responses against a melanoma tumor antigen.cytotoxic t cells represent a powerful strategy for antitumor treatment. depending on the route of injection, an important role for cd4 t cell-mediated help was observed in the induction of this response. for this reason, we investigated whether induction of a ctl response to the hla-a2-restricted immunodominant peptide melanoma antigen melan-a was improved by using rvvs expressing the ctl-defined epitope alone or in combination with an sag. in the latter case, the few infected dendritic cells s ...200211979434
ar possesses an intrinsic hormone-independent transcriptional activity.recent research has highlighted the functional importance of chromatin structure in transcriptional regulation. we have used xenopus oocytes as a model system to investigate the action of ar in the context of chromatin. by manipulating the levels of ar expression, we have observed both agonist-dependent and -independent activation by ar. expression of ar at relatively low levels resulted in strong agonist-dependent activation, whereas high levels of ar also led to hormone-independent activation. ...200211981028
the effect of dna-alkylating agents on gene expression from two integrated reporter genes in a mouse mammary tumor line.a model system was developed to investigate the effects of dna alkylating agents on cellular gene expression. the cytomegalovirus immediate-early promoter (cmv) and the mouse mammary tumor virus promoter (mmtv) were coupled separately to the luciferase reporter gene and stably expressed in cultured cells. the change in luciferase activity was used as a measure of gene expression inhibition. seven well-characterized dna alkylating agents of varied dna adduct-forming ability were evaluated in this ...200211984071
dependence of selective gene activation on the androgen receptor nh2- and cooh-terminal interaction.the agonist-induced androgen receptor nh(2)- and cooh-terminal (n/c) interaction is mediated by the fxxlf and wxxlf nh(2)-terminal motifs. here we demonstrate that agonist-dependent transactivation of prostate-specific antigen (psa) and probasin enhancer/promoter regions requires the n/c interaction, whereas the sex-limited protein gene and mouse mammary tumor virus long terminal repeat do not. transactivation of psa and probasin response regions also depends on activation function 1 (af1) in th ...200212000757
inducible dimerization of fgfr1: development of a mouse model to analyze progressive transformation of the mammary gland.to develop an inducible and progressive model of mammary gland tumorigenesis, transgenic mice were generated with a mouse mammary tumor virus-long terminal repeat-driven, conditional, fibroblast growth factor (fgf)-independent fgf receptor (fgfr)1 (ifgfr1) that can be induced to dimerize with the drug ap20187. treatment of transgenic mice with ap20187 resulted in ifgfr1 tyrosine phosphorylation, increased proliferation, activation of mitogen-activated protein kinase and akt, and lateral budding. ...200212011115
wnt3-wnt14b and wnt3a-wnt14 gene clusters (review).wnt signals are transduced to beta-catenin - tcf pathway, jnk pathway, or ca2+-releasing pathway through wnt receptors. frat1, frat2, and par-1 are positive regulators of wnt - beta-catenin pathway. apc, axin, nkd1, nkd2, and strabismus (stb1, stb2) are negative regulators of wnt - beta-catenin pathway. here, biological significance of wnt3-wnt14b/wnt15 gene cluster (human chromosome 17q21) and wnt3a-wnt14 gene cluster (human chromosome 1q42) will be reviewed. total-amino-acid identity between w ...200212011973
lack of ductal development in the absence of functional estrogen receptor alpha delays mammary tumor formation induced by transgenic expression of erbb2/neu.expression of the mouse mammary tumor virus (mmtv) neu/erbb2 transgene in mice induces mammary tumors. to examine the effect of removing estrogen receptor alpha (eralpha) signaling on the ability of an mmtv-neu/erbb2 transgene to induce mammary tumors, the neu transgene was expressed in the eralpha knockout (alphaerko) mouse, which lacks functional eralpha. mmtv-neu females that lacked eralpha still developed mammary tumors; however, tumor onset was significantly delayed. this study indicates th ...200212019156
proteasomal inhibition enhances glucocorticoid receptor transactivation and alters its subnuclear trafficking.the ubiquitin-proteasome pathway regulates the turnover of many transcription factors, including steroid hormone receptors such as the estrogen receptor and progesterone receptor. for these receptors, proteasome inhibition interferes with steroid-mediated transcription. we show here that proteasome inhibition with mg132 results in increased accumulation of the glucocorticoid receptor (gr), confirming that it is likewise a substrate for the ubiquitin-proteasome degradative pathway. using the mous ...200212024025
inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model.maspin has been shown to possess tumor-suppressing activity against breast tumor growth and metastasis. to test the therapeutic value of the maspin gene (serpinb5) in breast cancer, we established a syngeneic breast tumor metastasis model. this model involved the implantation of mammary tumor cells orthotopically to mammary gland and allowed tumors to grow within the gland and become metastatic to other organs. the mammary tumor cells were initially isolated from mmtv-polyoma virus middle t tran ...200212027560
glucocorticoid receptor domain requirements for chromatin remodeling and transcriptional activation of the mouse mammary tumor virus promoter in different nucleoprotein contexts.the glucocorticoid receptor (gr) contains several activation domains, tau1 (af-1), tau2, and af-2, which were initially defined using transiently transfected reporter constructs. using domain mutations in the context of full-length gr, this study defines those domains required for activation of the mouse mammary tumor virus (mmtv) promoter in two distinct nucleoprotein configurations. a transiently transfected mmtv template with a disorganized, accessible chromatin structure was largely dependen ...200212029095
activity of the gr in g2 and mitosis.to elucidate the mechanisms mediating the reported transient physiological glucocorticoid resistance in g2/m cell cycle phase, we sought to establish a model system of glucocorticoid-resistant cells in g2. we synchronized various cell lines in g2 to measure dexamethasone (dex)-induced transactivation of either two endogenous promoters (rat tyrosine aminotransferase and mouse metallothionein i) or the mouse mammary tumor virus (mmtv) promoter stably or transiently transfected. to circumvent the n ...200212040020
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