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prevalence of mouse mammary tumor virus (mmtv) in wild house mice (mus musculis) in southeastern australia.we determined the prevalence of mouse mammary tumor virus (mmtv) in introduced, free-roaming, wild house mice (mus musculus domesticus) [corrected] and compared envelope (env) and long terminal repeat (ltr) nucleotide sequences of viruses from wild mice and other sources. mice were trapped on two occasions, in october (spring) and the following may (autumn) of 2003-2004 in the mallee region of northwestern victoria, australia. animals were assigned to three cohorts (subadult, young, and old adul ...200717984262
a novel block to mouse mammary tumor virus infection of lymphocytes in b10.br mice.classic studies on c57bl-derived mouse strains showed that they were resistant to mouse mammary tumor virus (mmtv) infection. although one form of resistance mapped to the major histocompatibility complex (mhc) locus, at least one other, unknown gene was implicated in this resistance. we show here that b10.br mice, which are derived from c57bl mice but have the same mhc locus (h-2(k)) as susceptible c3h/hen mice, are resistant to mmtv, and show a lack of virus spread in their lymphoid compartmen ...200818003725
a novel flk1-tva transgenic mouse model for gene delivery to angiogenic vasculature.the genes that regulate the formation of blood vessels in adult tissues represent promising therapeutic targets because angiogenesis plays a role in many diseases, including cancer. we wished to develop a mouse model allowing characterization of gene function in adult angiogenic vasculature while minimizing effects on embryonic vasculature or adult quiescent vasculature. here we describe a transgenic mouse model that allows expression of proteins in the endothelial cells of newly forming blood v ...200818027100
mouse mammary tumor virus integration site selection in human and mouse genomes.based on integration site preferences, retroviruses can be placed into three groups. viruses that comprise the first group, murine leukemia virus and foamy virus, integrate preferentially near transcription start sites. the second group, notably human immunodeficiency virus and simian immunodeficiency virus, preferentially targets transcription units. avian sarcoma-leukosis virus (aslv) and human t-cell leukemia virus (htlv), forming the third group, show little preference for any genomic featur ...200818032509
mammary alveolar development during lactation is inhibited by the endogenous antiangiogenic growth factor isoform, vegf165b.extensive tissue remodeling occurs in breast tissue during pregnancy, resulting in growth and development of the mammary gland associated with extensive vascular remodeling, which is thought to be dependent on vascular endothelial growth factor (vegf). we show here that the endogenous antiangiogenic splice isoform of vegf, vegf(165)b, is normally expressed in nonlactating human and mouse breast, and is down-regulated in wt mice during lactation. to demonstrate the physiological role of vegf(165) ...200818032632
nonsteroidal glucocorticoid agonists: tetrahydronaphthalenes with alternative steroidal a-ring mimetics possessing dissociated (transrepression/transactivation) efficacy selectivity.the synthesis and biological activity of tetrahydronaphthalene derivatives coupled to various heterocycles are described. these compounds are potent glucocorticoid receptor agonists with efficacy selectivity in an nfkappab glucocorticoid receptor (gr) agonist assay (representing transrepression effects) over an mmtv gr agonist assay (representing transactivation effects). quinolones, indoles, and c- and n-linked quinolines are some of the heterocycles that provide efficacy selectivity. for examp ...200718038970
effects of some new antiepileptic drugs and progabide on glucocorticoid receptor-mediated gene transcription in lmcat cells.antiepileptic drugs affect endocrine and immune system activity, however, it is not clear whether these effects are indirect, via interference with neurotransmitters, membrane receptors and ion channels or maybe independent of neuronal mechanisms. in order to shed more light on this problem, in the present study, we evaluated effects of some new-generation antiepileptic drugs and progabide as a gaba-mimetic on the corticosterone-induced chloramphenicol acetyltransferase (cat) activity in mouse f ...200718048953
amino-biphosphonate-mediated mmp-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma.balb-neut mice expressing an activated rat c-erbb-2/neu transgene under the mouse mammary tumor virus long terminal repeat show enhanced hematopoiesis with hyperproduction of myeloid-derived suppressor cells (mdsc) because of vascular endothelial growth factor (vegf) secreted by the tumor. here, we show that both tumor and stromal cells express matrix metalloproteinase-9 (mmp-9), thereby increasing the levels of pro-mmp-9 in the sera of tumor-bearing mice. treatment with amino-biphosphonates imp ...200718056472
replication of beta- and gammaretroviruses is restricted in i/lnj mice via the same genetic mechanism.mice of the i/lnj inbred strain are unique in their ability to mount a robust and sustained humoral immune response capable of neutralizing infection with a betaretrovirus, mouse mammary tumor virus (mmtv). virus-neutralizing antibodies (abs) coat mmtv virions secreted by infected cells, preventing virus spread and hence the formation of mammary tumors. to investigate whether i/lnj mice resist infection with other retroviruses besides mmtv, the animals were infected with murine leukemia virus (m ...200818057254
analyses of the role of endogenous sparc in mouse models of prostate and breast cancer.secreted protein, acidic and rich in cysteine (sparc, also known as osteonectin or bm-40) is a glycoprotein component of the extracellular matrix that has been reported to be involved with a variety of cellular processes. although sparc expression levels are frequently altered in a variety of tumor types, the exact implications of deregulated sparc expression--whether it promotes, inhibits or has no effect on tumor progression--have remained unclear. our recent gene expression analyses have show ...200818058030
mt1-mmp is required for efficient tumor dissemination in experimental metastatic disease.membrane-type i matrix metalloproteinase (mt1-mmp) is associated with multiple forms of cancer including mammary cancer. to directly evaluate the significance of mt1-mmp expression in tumor progression and metastasis using a genetically induced cancer model, we crossed mt1-mmp-deficient mice to mmtv-polyoma virus middle t-antigen (pymt) mice. expression of pymt in the mt1-mmp-deficient background consistently resulted in hyperplasia of the mammary gland as seen in wild-type pymt littermates. fol ...200818071307
variable transcriptional activity of endogenous retroviruses in human breast cancer.human endogenous retroviruses (hervs) account for up to 9% of the human genome and include more than 800 elements related to betaretroviruses. while mouse mammary tumor virus (mmtv) is the accepted etiological agent of mammary tumors in mice, the role of retroviral elements in human breast cancer remains elusive. here, we performed a comprehensive microarray-based analysis of overall retroviral transcriptional activities in 46 mammary gland tissue specimens representing pairs of nonmalignant and ...200818077721
the hsa domain of brg1 mediates critical interactions required for glucocorticoid receptor-dependent transcriptional activation in vivo.the packaging of eukaryotic dna into chromatin can create an impediment to transcription by hindering binding of essential factors required for transcription. the mammalian swi/snf remodeling complex has been shown to alter local chromatin structure and facilitate recruitment of transcription factors. brg1 (or hbrm), the central atpase of the human swi/snf complex, is a critical factor for the functional activity of nuclear receptor complexes. analysis using brg1/snf2h chimeras suggests brg1 may ...200818086889
bcl-2 and mutant nras interact physically and functionally in a mouse model of progressive myelodysplasia.myelodysplastic syndromes (mds) are clonal stem cell hematologic disorders that evolve to acute myeloid leukemia (aml) and thus model multistep leukemogenesis. activating ras mutations and overexpression of bcl-2 are prognostic features of mds/aml transformation. using nrasd12 and bcl-2, we created two distinct models of mds and aml, where human (h)bcl-2 is conditionally or constitutively expressed. our novel transplantable in vivo models show that expression of hbcl-2 in a primitive compartment ...200718089795
bioluminescence imaging of vascular endothelial growth factor promoter activity in murine mammary tumorigenesis.vascular endothelial growth factor (vegf) is a major inducer of angiogenesis. we generated a transgenic reporter mouse, vegf-gl, in which an enhanced green fluorescent protein-luciferase fusion protein is expressed under the control of a human vegf-a promoter. the vegf-gl mouse exhibited intense bioluminescence throughout the body at 1 week of age. the signals rapidly declined to a relatively low level as the mice grew. the adult vegf-gl mouse showed restricted bioluminescence to the areas under ...200718092518
altered histone h1 stoichiometry and an absence of nucleosome positioning on transfected dna.the packaging of dna with histones to form chromatin represents an important and powerful mechanism to regulate gene expression. critical aspects of chromatin-specific contributions to gene regulation have been revealed by the comparison of the activities from dna regulatory elements examined both as transiently transfected reporters and stably integrated reporters organized as chromatin. using the mouse mammary tumor virus (mmtv) promoter as a model, we probed the structural differences between ...200818156629
pleiotrophin, a multifunctional tumor promoter through induction of tumor angiogenesis, remodeling of the tumor microenvironment, and activation of stromal fibroblasts.pleiotrophin (ptn, ptn) is a widely expressed, developmentally regulated 136 amino acid secreted heparin-binding cytokine. it signals through a unique signaling pathway; the ptn receptor is the transmembrane receptor protein tyrosine phosphatase (rptp)beta/zeta. rptpbeta/zeta is inactivated by ptn, which leads to increased tyrosine phosphorylation of the downstream targets of the ptn/rptpbeta/zeta signaling pathway. pleiotrophin gene expression is found in cells in early differentiation during d ...200718156802
erbb-2 receptor cooperates with e6/e7 oncoproteins of hpv type 16 in breast tumorigenesis.the erbb-2 receptor is overexpressed in roughly 30% of human breast cancers. moreover, approximately 50% of breast cancers are positive for high-risk human papillomaviruses (hpvs), specifically types 16 and 18. recently, we reported that erbb-2 cooperates with e6/e7 oncoproteins of hpv type 16 to induce neoplastic transformation of human normal oral epithelial cells. we also demonstrated that e6/e7 of hpv type 16 converts non-invasive breast cancer cells to an invasive form. in order to investig ...200718156804
alpha 2-6-linked sialic acids on n-glycans modulate carcinoma differentiation in vivo.sialic acids on vertebrate cell surfaces mediate many biological roles. altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. a classic but unexplained example is enhanced alpha2-6-sialylation on n-glycans resulting from overexpression of the golgi enzyme beta-galactoside:alpha2-6-sialyltransferase (st6gal-i). previous data supporting a role for the resulting sia alpha 2-3gal beta 1-4glcnac (sia6lacnac) structure in tumor biology were ...200818199532
regulation of cripto-1 signaling and biological activity by caveolin-1 in mammary epithelial cells.human and mouse cripto-1 (cr-1/cr-1) proteins play an important role in mammary gland development and tumorigenesis. in this study, we examined the relationship between cripto-1 and caveolin-1 (cav-1), a membrane protein that acts as a tumor suppressor in the mammary gland. cripto-1 was found to interact with cav-1 in cos7 cells and mammary epithelial cells. using eph4 mouse mammary epithelial cells expressing cr-1 (eph4 cr-1) or cr-1 and cav-1 (eph4 cr-1/cav-1), we demonstrate that cav-1 expres ...200818202186
src kinase potentiates androgen receptor transactivation function and invasion of androgen-independent prostate cancer c4-2 cells.prostate cancer is one of the most prominent malignancies of elderly men in many western countries including europe and the united states with increasing trend worldwide. the growth of normal prostate as well as of prostate carcinoma cells depends on functional androgen receptor (ar) signaling. ar manifests the biological actions of androgens and its transcriptional activity is known to be influenced by signal transduction pathways. here we show that src, a nonreceptor tyrosine kinase, is overex ...200818223692
interactive effects of selenium and cadmium on mammary tumor development and growth in mmtv-infected female mice. a model study on the roles of cadmium and selenium in human breast cancer.previous studies demonstrated that the age-corrected breast cancer mortalities in different countries are inversely correlated with the per-capita dietary intakes of selenium and directly with the estimated intakes of cadmium, zinc, and chromium, suggesting that the anticarcinogenic properties of selenium are counteracted by these elements. the tumor-preventative effects of selenium and the converse effects zinc and chromium have already been confirmed experimentally in studies with female inbre ...200818264682
trail-related neurotoxicity implies interaction with the wnt pathway in human neuronal cells in vitro.tumor necrosis factor related apoptosis inducing ligand (trail) is involved in amyloid beta dependent neurotoxicity via the extrinsic pathway. recently, several genes modulating trail cytotoxicity have been characterized, providing evidence for a role of wingless-type mouse mammary tumor virus integration site family (wnt), jun-n-terminal kinase and other pathways in increased cell susceptibility to the cytokine. we investigated whether neurotoxic effects of trail could be due to modulation of t ...200818266928
the signal peptide of the mouse mammary tumor virus rem protein is released from the endoplasmic reticulum membrane and accumulates in nucleoli.n-terminal signal sequences mediate endoplasmic reticulum (er) targeting and insertion of nascent secretory and membrane proteins and are, in most cases, cleaved off by signal peptidase. the mouse mammary tumor virus envelope protein and its alternative splice variant rem have an unusually long signal sequence, which contains a nuclear localization signal. although the envelope protein is targeted to the er, inserted, and glycosylated, rem has been described as a nuclear protein. rem as well as ...200818270201
comparison of expression profiles of metastatic versus primary mammary tumors in mmtv-wnt-1 and mmtv-neu transgenic mice.distant metastases of human breast cancers have been suggested to be more different from each other than from their respective primary tumors, based on expression profiling. the mechanism behind this lack of similarity between individual metastases is not known. we used cdna microarrays to determine the expression profiles of pulmonary metastases and primary mammary tumors in two distinct transgenic models expressing either the neu or the wnt-1 oncogene from the mouse mammary tumor virus long te ...200818283333
genotype x diet interactions in mice predisposed to mammary cancer. i. body weight and fat.high dietary fat intake and obesity may increase susceptibility to certain forms of cancer. to study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of f(2) mice cosegregating obesity qtl and the mmtv-pymt transgene. we fed the f(2) mice either a very-high-fat or a matched-control-fat diet and measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. snp genotyping across the g ...200818286334
the gln family of murine endogenous retroviruses contains an element competent for infectious viral particle formation.several families of endogenous retroviruses (ervs) have been identified in the mouse genome, in several instances by in silico searches, but for many of them it remains to be determined whether there are elements that can still encode functional retroviral particles. here, we identify, within the gln family of highly reiterated ervs, one, and only one, copy that encodes retroviral particles prone to infection of mouse cells. we show that its envelope protein confers an ecotropic host range and r ...200818287236
genotype x diet interactions in mice predisposed to mammary cancer: ii. tumors and metastasis.high dietary fat intake and obesity may increase the risk of susceptibility to certain forms of cancer. to study the interactions of dietary fat, obesity, and metastatic mammary cancer, we created a population of f(2) mice cosegregating obesity qtl and the mmtv-pymt transgene. we fed the f(2) mice either a very high-fat or a matched-control-fat diet, and we measured growth, body composition, age at mammary tumor onset, tumor number and severity, and formation of pulmonary metastases. snp genotyp ...200818288525
androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell.androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. the acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. however, rat prostate endothelial cells were reported not to express androgen receptor (ar), and the role of the androgen axis in human prostate endothelial cell (hpec) homeostasis was poorly characterized. in this study ar expression was de ...200818292195
mouse mammary tumor virus (mmtv)-like dna sequences in the breast tumors of father, mother, and daughter.the diagnosis of late onset breast cancer in a father, mother, and daughter living in the same house for decades suggested the possibility of an environmental agent as a common etiological factor. both molecular and epidemiological data have indicated a possible role for the mouse mammary tumor virus (mmtv), the etiological agent of breast cancer in mice, in a certain percentage of human breast tumors. the aim of this study was to determine if mmtv might be involved in the breast cancer of this ...200818307792
thermodynamic dissection of progesterone receptor interactions at the mouse mammary tumor virus promoter: monomer binding and strong cooperativity dominate the assembly reaction.progesterone receptors (prs) play critical roles in eukaryotic gene regulation, yet the mechanisms by which they assemble at their promoters are poorly understood. one of the few promoters amenable to analysis is the mouse mammary tumor virus gene regulatory sequence. embedded within this sequence are four progesterone response elements (pres) corresponding to a palindromic pre and three half-site pres. early mutational studies indicated that the presence of all four sites generated a synergisti ...200818313072
t-cadherin supports angiogenesis and adiponectin association with the vasculature in a mouse mammary tumor model.t-cadherin delineates endothelial, myoepithelial, and ductal epithelial cells in the normal mouse mammary gland, and becomes progressively restricted to the vasculature during mammary tumorigenesis. to test the function of t-cadherin in breast cancer, we inactivated the t-cadherin (cdh13) gene in mice and evaluated tumor development and pathology after crossing the mutation into the mouse mammary tumor virus (mmtv)-polyoma virus middle t (pyv-mt) transgenic model. we report that t-cadherin defic ...200818316604
rad6b is a positive regulator of beta-catenin stabilization.mutations in beta-catenin or other wnt pathway components that cause beta-catenin accumulation occur rarely in breast cancer. however, there is some evidence of beta-catenin protein accumulation in a subset of breast tumors. we have recently shown that rad6b, an ubiquitin-conjugating enzyme, is a transcriptional target of beta-catenin/tcf. here, we show that forced rad6b overexpression in mcf10a breast cells induces beta-catenin accumulation, which despite being ubiquitinated is stable and trans ...200818339854
transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment.transforming growth factor (tgf)-beta signaling has been associated with early tumor suppression and late tumor progression; however, many of the mechanisms that mediate these processes are not known. using cre/loxp technology, with the whey acidic protein promoter driving transgenic expression of cre recombinase (wap-cre), we have now ablated the type ii tgf-beta receptor (t beta rii) expression specifically within mouse mammary alveolar progenitors. transgenic expression of the polyoma virus m ...200818339861
mouse mammary tumor virus-like env sequences in human breast cancer.mouse mammary tumor virus (mmtv) has long been known as a causal agent of breast cancer in mice. to date, varied mmtv-like envelope gene (env) sequences have been identified in up to 74% of human breast cancers. however, the role and origin of these mmtv-like sequences in human breast cancer remain uncertain. our study was initiated to study the integration of mmtv-like env sequences in human breast cancer. pcr screening has identified 28 (56%) australian breast cancer specimens and 7 (87.5%) hu ...200818348144
the rexinoid, bexarotene, prevents the development of premalignant lesions in mmtv-erbb2 mice.retinoids, vitamin a analogues that bind to retinoic acid receptor (rar) or retinoid x receptor (rxr), play important roles in regulating cell proliferation, apoptosis, and differentiation. recently, rxr-selective ligands, also referred to as rexinoids, have been investigated as potential chemopreventive agents for breast cancer. our previous studies demonstrated that the rexinoid bexarotene significantly prevented er-negative mammary tumourigenesis with less toxicity than naturally occurring re ...200818362934
lentiviral transduction of mammary stem cells for analysis of gene function during development and cancer.the mouse mammary gland is the only epithelial organ capable of complete regeneration upon orthotopic transplantation, making it ideally suited for in vivo gene function studies through viral-mediated gene delivery. a hurdle that has challenged the widespread adoption of this technique has been the inability to transduce mammary stem cells effectively. we have overcome this limitation by infecting total primary mammary epithelial cells in suspension with high-titer lentiviruses. transduced cells ...200818371425
mouse mammary tumor virus promoter-containing retroviral promoter conversion vectors for gene-directed enzyme prodrug therapy are functional in vitro and in vivo.gene directed-enzyme prodrug therapy (gdept) is an approach for sensitization of tumor cells to an enzymatically activated, otherwise nontoxic, prodrug. cytochrome p450 2b1 (cyp2b1) metabolizes the prodrugs cyclophosphamide (cpa) and ifosfamide (ifa) to produce the cytotoxic substances phosphoramide mustard and isophosphoramide mustard as well as the byproduct acrolein. we have constructed a retroviral promoter conversion (procon) vector for breast cancer gdept. the vector allows expression of c ...200818414588
mmtv-cre-mediated fur inactivation concomitant with plag1 proto-oncogene activation delays salivary gland tumorigenesis in mice.proprotein convertases are serine endoproteases implicated in the proteolytic processing of a large variety of regulatory proteins. an important role of proprotein convertases in tumorigenic processes has been suggested by various studies. in this study, the role of the proprotein convertase furin in plag1 proto-oncogene-induced salivary gland tumorigenesis was investigated. plag1 overexpression in salivary glands has previously been shown to result in salivary gland tumors in 100% of mice withi ...200818425334
mouse endogenous superantigens: ms and mls-like determinants encoded by mouse retroviruses.commonly used inbred mouse strains express different combinations of integrated mouse mammary tumor proviruses (mmtv). this appendix summarizes the proviruses that have been detected. the reported functional properties of those mmtv proviral products which have been identified as superantigens are also summarized, including the ability to elicit primary or secondary t cell responses and to induce vb-specific clonal deletion during t cell differentiation. in addition, the amino acid sequences of ...200118432642
effect of some antidepressants on the low corticosterone concentration-induced gene transcription in lmcat fibroblast cells.the aim of the present study was to investigate effects of some classical and new antidepressants on functional activity of the glucocorticoid receceptor (gr) induced by low corticosterone concentration in mouse fibroblast cells stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase plasmid (lmcat cells). we found that the transcriptional activity of gr stimulated by 50 nm corticosterone was strongly attenuated by imipramine, desipramine, fluoxetine and tianeptine in ...200818441395
other potential medical therapies: the use of antiviral agents to investigate and treat primary ciliary cirrhosis.a human betaretrovirus has been characterized in patients with primary biliary cirrhosis (pbc) and the related mouse mammary tumor virus linked with autoimmune biliary disease in the nod.c3c4 mouse model. translational studies have been performed in patients who have pbc to investigate the role of viral infection in disease. patients treated with combivir experienced significant improvements in hepatic biochemistry, clinical symptoms, and histology with evidence of reversal of ductopenia. prelim ...200818456190
hoxb7 inhibits transgenic her-2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis.our previous studies have shown that hoxb7 mrna is overexpressed in approximately 50% of invasive breast carcinomas and promotes tumor progression in breast cancer cells grown as xenografts in mice. in silico analysis of published microarray data showed that high levels of hoxb7 predict a poor outcome in her-2-positive (p = 0.046), but not in her-2-negative breast cancers (p = 0.94). to study the function of hoxb7 in vivo in the context of her-2 overexpression, we generated mouse mammary tumor v ...200818463397
mutations in the c-terminus of the x protein of hepatitis b virus regulate wnt-5a expression in hepatoma huh7 cells: cdna microarray and proteomic analyses.the hepatitis b virus x gene (hbx) is a promiscuous transactivator implicated in the development of hepatocellular carcinoma (hcc). the present study was designed to investigate the molecular events regulated by hbx.200818477650
early increases in superantigen-specific foxp3+ regulatory t cells during mouse mammary tumor virus infection.mouse mammary tumor virus (mmtv) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. here, we show in a natural model of mmtv infection that the virus causes early and progressive increases in superantigen (sag)-specific foxp3(+) regulatory t cells (t(reg)) in peyer's patches (pp). these increases were shown to be dependent on the presence of dendritic cells. cd4(+) cd25(+) t cells from the pp of infected mice preferentially suppress the pr ...200818495774
chromatin remodeling complexes interact dynamically with a glucocorticoid receptor-regulated promoter.brahma (brm) and brahma-related gene 1 (brg1) are the atp-dependent catalytic subunits of the swi/snf family of chromatin-remodeling complexes. these complexes are involved in essential processes such as cell cycle, growth, differentiation, and cancer. using imaging approaches in a cell line that harbors tandem repeats of stably integrated copies of the steroid responsive mmtv-ltr (mouse mammary tumor virus-long terminal repeat), we show that brg1 and brm are recruited to the mmtv promoter in a ...200818508913
a 5' distal palindrome within the mouse mammary tumor virus-long terminal repeat recruits a mammary gland-specific complex and is required for a synergistic response to progesterone plus prolactin.progesterone (p) and prolactin (prl) fulfill crucial roles during growth and differentiation of the mammary epithelium, and each has been implicated in the pathogenesis of mammary cancer. we previously identified that these hormones synergistically stimulate the proliferation of mouse mammary epithelial cells in vivo, although the mechanism(s) underlying their cooperative effect are unknown. we now report a novel pathway by which p and prl synergize to activate transcription from the long termin ...200818524869
no association of mouse mammary tumor virus-related retrovirus with japanese cases of breast cancer.mouse mammary tumor virus (mmtv) is the causative agent of breast tumors in mice. recently, dna sequences homologous or closely related to mmtv env gene have been specifically detected in breast cancer tissue from significant numbers of american, australian, and tunisian women, suggesting a viral etiology for at least a part of human breast cancer. however, the viral sequences have not been detected from any of breast cancer samples in several subsequent studies. thus, whether mmtv-related retro ...200818551605
germline mutation in rnasel predicts increased risk of head and neck, uterine cervix and breast cancer.the background: ribonuclease l (rnasel), encoding the 2'-5'-oligoadenylate (2-5a)-dependent rnase l, is a key enzyme in the interferon induced antiviral and anti-proliferate pathway. mutations in rnasel segregate with the disease in prostate cancer families and specific genotypes are associated with an increased risk of prostate cancer. infection by human papillomavirus (hpv) is the major risk factor for uterine cervix cancer and for a subset of head and neck squamous cell carcinomas (hnscc). hp ...200818575592
cranberry juice constituents impair lymphoma growth and augment the generation of antilymphoma antibodies in syngeneic mice.in addition to its nutritional value, cranberry juice has been effective in treating urinary tract infections. various reports have also demonstrated its potential for inhibiting in vitro growth of transformed cell lines. here we show that a fraction [nondialyzable material (ndm) of a molecular weight range 12,000-30,000 (ndm 12-30k)] derived from cranberry juice impairs in vitro growth and invasion through extracellular matrix of rev-2-t-6 murine lymphoma cells. furthermore, intraperitoneal inj ...200818584485
tiam1-deficiency impairs mammary tumor formation in mmtv-c-neu but not in mmtv-c-myc mice.rho-like small gtpases, including rhoa, rac1 and cdc42, are crucial for the regulation of a large variety of biological processes such as the cytoskeletal organization and gene transcription. the activities of rho gtpases are predominantly controlled by guanine nucleotide exchange factors (gefs), which activate gtpases by catalyzing the exchange of bound gdp for gtp. earlier, we have identified the tiam1 gene as an invasion-inducing gene that encodes a specific activator (gef) of the rac gtpase. ...200918592271
inability to predict mammary tumorigenesis in strain a mice from presence of mammary tumor virus or antigen in the milk.strain a females were milked and their milk was tested for mammary tumor virus (mtv) by the hyperplastic alveolar nodule test and for mtv antigen by microimmunodiffusion. an attempt was made to correlate these results with later occurrence of mammary tumors in the females. there was not full agreement between the results of the test for the presence of the mtv and those of the test for mtv antigen, and from these results it was impossible to predict accurately whether a specific female would lat ...197018605419
comments on: some aspects of the morphology of the bittner virus, by john k. clarke and joseph t. attridge, department of microbiology, the queen's university of belfast, belfast, bt12 6bn, northern ireland. j nat cancer inst 44: 755-762, 1970. 197018605435
effect of vitreoscilla hemoglobin expression on growth and specific tissue plasminogen activator productivity in recombinant chinese hamster ovary cells.previous studies suggest that secretion of cloned proteins synthesized by recombinant chinese hamster ovary (cho) cells can be adenosine triphosphate (atp) limited. other research indicates that the presence of cloned vitreoscilla hemoglobin (vhb) enhances atp production in oxygen-limited escherichia coli. to evaluate the influence of vhb expression on recombinant cho cell productivity, the vhb gene has been fused to the mouse mammary tumor virus (mmtv) promoter and cloned in a cho cell line pre ...199418618650
characteristics of the structural components of the mouse mammary tumor virus. ii. viral proteins and antigens.mild tween 80-ether treatment of mouse mammary tumor virus (mtv) results in disruption of the viral membrane and release of subviral components. prolonged lipid extraction, however, results in virtually complete solubilization of the virion. soluble proteins have been separated by sephadex g-200 chromatography and used for immunization of rats these antisera identify five viral antigens (designated mtv-s1, s2, s3, s4, and s5). the s1 and s2 antigens are group-specific, and are the antigens of th ...197118619368
gene order of the mouse mammary tumor virus glycoproteins.immunochemical and tryptic peptide mapping techniques were used to show that the mouse mammary tumor virus (mmtv) envelope glycoproteins gp52 and gp36 are distinct components derived from a common glycosylated precursor polypeptide of 75,000 daltons (gpr75). because both gp52 and gp36 are derived from a common precursor polypeptide and therefore have a common initiation site, we have been able to determine their gene order within the viral genome. the gene order was deduced from three different ...197718625476
cell cycle analysis of foreign gene (beta-galactosidase) expression in recombinant mouse cells under control of mouse mammary tumor virus promoter.the cell cycle dependency of foreign gene expression in recombinant mouse l cells was investigated. two different recombinant mouse l cell lines having the glucocorticoid receptor-encoding gene and the lacz reporter gene were used in this study. the lacz gene expression was controlled by the glucocorticoid-inducible mouse mammary tumor virus (mmtv) promoter in both cell lines. in "m4" cells the gr gene was under the control of another mmtv promoter, but in "r2" cells it was under the control of ...199618626950
prevention and treatment of experimental estrogen receptor-negative mammary carcinogenesis by the synthetic triterpenoid cddo-methyl ester and the rexinoid lg100268.to test whether the triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester (cddo-me) and the rexinoid lg100268 (268) prevent the formation of estrogen receptor (er)-negative mammary tumors or either arrest the growth or cause regression of established tumors in mmtv-neu mice.200818628471
immunology of the mouse mammary tumor virus: comparison of mammary tumor virus with the agent found in c3hf/crgl mice.c3hf/crgl mice, containing no biologically active mammary tumor virus, nonetheless possess both type-b virus particles and a component which cross-reacts serologically with the mammary tumor virus. neutralization studies and the immunodiffusion assay for measuring the antigenicity of the mammary tumor virus indicate that transfer of the virus particles from c3hf to balb/ccrgl mice is accompanied by transfer of the cross-reacting antigenic component.196618630318
mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression.maternal food restriction during pregnancy results in growth-restricted newborns and reduced glomerular number, contributing to programmed offspring hypertension. we investigated whether reduced nephrogenesis may be programmed by dysregulation of factors controlling ureteric bud branching and mesenchyme to epithelial transformation.200818639218
prevalence and characteristics of the mmtv-like associated breast carcinomas in tunisia.the involvement of a retrovirus homologous to the mouse mammary tumor virus (mmtv) in the pathogenesis of human breast cancer (bc) has long been assumed, but has never been proven. previous studies have reported the detection of mmtv-like env sequences in variable proportions that did not exceed 40% of bc cases in several countries. however, these viral sequences have been found in higher proportion (74%) in tunisian diagnosed with bc during the seventies. this study is an attempt to evaluate th ...200818639977
the aib1 oncogene promotes breast cancer metastasis by activation of pea3-mediated matrix metalloproteinase 2 (mmp2) and mmp9 expression.amplified-in-breast cancer 1 (aib1) is an overexpressed transcriptional coactivator in breast cancer. although overproduced aib1 is oncogenic, its role and underlying mechanisms in metastasis remain unclear. here, mammary tumorigenesis and lung metastasis were investigated in wild-type (wt) and aib1(-/-) mice harboring the mouse mammary tumor virus-polyomavirus middle t (pymt) transgene. all wt/pymt mice developed massive lung metastasis, but aib1(-/-)/pymt mice with comparable mammary tumors ha ...200818644862
mmtv-induced pregnancy-dependent mammary tumors : early history and new perspectives.almost 60 years ago, foulds carefully described for the first time a particular type of mouse mammary tumor that appeared in the glands of pregnant females and disappeared shortly after delivery. since then, the attention that researchers paid to the mouse mammary tumor virus (mmtv)-induced pregnancy-dependent tumors has not vanished through the years. this was because the information obtained from mice carrying mmtv variants that were able to induce pregnancy-dependent tumors was meaningful for ...200818661103
mmtv infectious cycle and the contribution of virus-encoded proteins to transformation of mammary tissue.mouse mammary tumor virus has served as a major model for the study of breast cancer since its discovery 1920's as a milk-transmitted agent. much is known about in vivo infection by this virus, which initially occurs in lymphocytes that then carry virus to mammary tissue. in addition to the virion proteins, mmtv encodes a number of accessory proteins that facilitate high level in vivo infection. high level infection of lymphoid and mammary epithelial cells ensures efficient passage of virus to t ...200818661104
premalignant and malignant mammary lesions induced by mmtv and chemical carcinogens.this article reviews the types of mammary premalignant and malignant lesions induced in the mouse mammary gland after exposure to mmtv and chemical carcinogens. there are different morphological types of hyperplastic lesions in the mouse mammary gland. these lesions are designated as alveolar hyperplasia (han), ductal hyperplasia (dh), and cystic lesions; both non-keratinized and keratinized. the han and dh have been demonstrated to be precursors to invasive lesions. the han as a group tend to b ...200818663563
winding roots of wnts.several factors contributed to the discovery of wnt genes. on the one hand, the development of research tools in mammalian genetics such as mouse strains with high incidence of cancer in 1920-1930s led to discovery of the mouse mammary tumor virus in 1949. this virus in turn was used in 1982 to identify int-1 (wnt1) in mammals. on the other hand, a discovery of the wingless mutant in 1973 resulted in cloning of the wingless (wg) gene in 1987. a comparative analysis of int-1 and wg led to the rea ...200818694330
matrix metalloproteinase 13 is induced in fibroblasts in polyomavirus middle t antigen-driven mammary carcinoma without influencing tumor progression.matrix metalloproteinase (mmp) 13 (collagenase 3) is an extracellular matrix remodeling enzyme that is induced in myofibroblasts during the earliest invasive stages of human breast carcinoma, suggesting that it is involved in tumor progression. during progression of mammary carcinomas in the polyoma virus middle t oncogene mouse model (mmtv-pymt), mmp13 mrna was strongly upregulated concurrently with the transition to invasive and metastatic carcinomas. as in human tumors, mmp13 mrna was found i ...200818698413
activated akt1 accelerates mmtv-c-erbb2 mammary tumourigenesis in mice without activation of erbb3.erbb2, a member of the epidermal growth factor receptor (egfr) family, is overexpressed in 20% to 30% of human breast cancer cases and forms oncogenic signalling complexes when dimerised to erbb3 or other egfr family members.200818700973
amino acid preferences of retroviral proteases for amino-terminal positions in a type 1 cleavage site.the specificities of the proteases of 11 retroviruses were studied using a series of oligopeptides with amino acid substitutions in the p1, p3, and p4 positions of a naturally occurring type 1 cleavage site (val-ser-gln-asn-tyr downward arrowpro-ile-val-gln) in human immunodeficiency virus type 1 (hiv-1). previously, the substrate specificity of the p2 site was studied for the same representative set of retroviral proteases, which included at least one member from each of the seven genera of the ...200818701588
[transcription factors of the nuclear factor 1 (nf1) family. role in chromatin remodelation].site-specific transcription factors of the nuclear factor 1 (nf1) family are ubiquitous, are encoded by four genes in mammals, and play a role in regulating transcription of approximately 100 cell and viral genes. the nf1 proteins are characterized by the ability to act as both transcription factors and viral replication factors and by a low affinity for nucleosomal dna. the review considers the dual role of the nf1 family factors in hormone-mediated transactivation of mouse mammary tumor virus ...200818702298
nucleosomal stability and dynamics vary significantly when viewed by internal versus terminal labels.nucleosomes are a major impediment to regulatory factor activities and therefore to the operation of genomic processes in eukaryotes. one suggested mechanism for overcoming in vivo nucleosomal repression is factor-mediated removal of h2a/h2b from nucleosomes. using nucleosomes labeled internally with fret fluorophores, we previously observed significant, dna sequence-dependent variation in stability and dynamics under conditions (subnanomolar concentrations) reported to produce h2a/h2b release f ...200818702521
common integration sites for mmtv in viral induced mouse mammary tumors.the paradigm of mammary cancer induction by the mouse mammary tumor virus (mmtv) is used to illustrate the body of evidence that supports the hypothesis that mammary epithelial stem/progenitor cells represent targets for oncogenic transformation. it is argued that this is not a special case applicable only to mmtv-induced mammary cancer, because mmtv acts as an environmental mutagen producing random interruptions in the somatic dna of infected cells by insertion of proviral dna copies. in additi ...200818709449
trial of the cysteine cathepsin inhibitor jpm-oet on early and advanced mammary cancer stages in the mmtv-pymt-transgenic mouse model.recent data suggest proteases of the papain-like cysteine cathepsin family as molecular targets for cancer therapy. here, we report the treatment of polyoma middle t oncogene-induced breast cancers in mice with the cell-permeable broad-spectrum cysteine cathepsin inhibitor jpm-oet. up to 100 mg/kg inhibitor was intraperitoneally injected once per day in two trials on early and advanced cancers. in both trials, transient delays in tumour growth were observed. however, at the endpoint of both expe ...200818710344
the mouse as a model for mammary tumorigenesis: history and current aspects. 200818712586
effects of selenium and low levels of lead on mammary tumor development and growth in mmtv-infected female mice.selenium (se) has been demonstrated in previous studies to inhibit mammary tumorigenesis in c3h mice infected with the murine mammary tumorvirus, mmtv. the antitumorigenic effects of se in this animal model of breast cancer were subsequently shown to be counteracted by se-antagonistic elements. lead (pb), for example, was found to abolish the anticarcinogenic effects of se at 5 ppm in the drinking water. the present study was undertaken to explore the effects of pb at just 0.5 ppm in the water, ...200818726561
protease-activated receptor (par) 2, but not par1, signaling promotes the development of mammary adenocarcinoma in polyoma middle t mice.the g protein-coupled protease-activated receptors (par) are key signaling components for proteases in vascular biology and tumor progression. to address the contributions of par1 and par2 to breast cancer development, we established cohorts of mouse mammary tumor virus-polyoma middle t (pymt) par1(-/-) and par2(-/-) mice, considering that the pymt model recapitulates aspects of human disease. appearance of palpable tumors, tumor expansion, and metastasis was indistinguishable between wild-type ...200818757438
expression profile of micrornas in c-myc induced mouse mammary tumors.c-myc is a transcription factor overexpression of which induces mammary cancer in transgenic mice. to explore whether certain micrornas (mirrna) mediate c-myc induced mammary carcinogenesis, we studied mirrna expression profile in mammary tumors developed from mmtv-c-myc transgenic mice, and found 50 and 59 mirrnas showing increased and decreased expression, respectively, compared with lactating mammary glands of wild type mice. twenty-four of these mirrnas could be grouped into eight clusters b ...200918777135
mouse apobec3 restricts friend leukemia virus infection and pathogenesis in vivo.several members of the apolipoprotein b mrna-editing enzyme catalytic polypeptide-like complex 3 (apobec3) family in primates act as potent inhibitors of retroviral replication. however, lentiviruses have evolved mechanisms to specifically evade host apobec3. likewise, murine leukemia viruses (mulv) exclude mouse apobec3 from the virions and cleave virion-incorporated apobec3. although the betaretrovirus mouse mammary tumor virus has been shown to be susceptible to mouse apobec3, it is not known ...200818786991
establishment and quantitative imaging of a 3d lung organotypic model of mammary tumor outgrowth.the lung is the second most common site of metastatic spread in breast cancer and experimental evidence has been provided in many systems for the importance of an organ-specific microenvironment in the development of metastasis. to better understand the interaction between tumor and host cells in this important secondary site, we have developed a 3d in vitro organotypic model of breast tumor metastatic growth in the lung. in our model, cells isolated from mouse lungs are placed in a collagen spo ...200818787962
metastasis is strongly reduced by the matrix metalloproteinase inhibitor galardin in the mmtv-pymt transgenic breast cancer model.matrix metalloproteinases (mmp) have several roles that influence cancer progression and dissemination. however, low molecular weight metalloproteinase inhibitors (mpi) have not yet been tested in transgenic/spontaneous metastasis models. we have tested galardin/gm6001, a potent mpi that reacts with most mmps, in the mmtv-pymt transgenic breast cancer model. we followed a cohort of 81 mmtv-pymt transgenic mice that received galardin, placebo, or no treatment. galardin treatment was started at ag ...200818790756
a novel point mutation in the amino terminal domain of the human glucocorticoid receptor (hgr) gene enhancing hgr-mediated gene expression.context: interindividual variations in glucocorticoid sensitivity have been associated with manifestations of cortisol excess or deficiency and may be partly explained by polymorphisms in the human glucocorticoid receptor (hgr) gene. we studied a 43-yr-old female, who presented with manifestations consistent with tissue-selective glucocorticoid hypersensitivity. we detected a novel, single, heterozygous nucleotide (g --> c) substitution at position 1201 (exon 2) of the hgr gene, which resulted i ...200818827003
mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low ph compartment and infect cells.mouse mammary tumor virus (mmtv) is a ph-dependent virus that uses mouse transferrin receptor 1 (tfr1) for entry into cells. previous studies demonstrated that mmtv could induce ph 5-dependent fusion-from-with of mouse cells. here we show that the mmtv envelope-mediated cell-cell fusion requires both the entry receptor and low ph (ph 5). although expression of the mmtv envelope and tfr1 was sufficient to mediate low ph-dependent syncytia formation, virus infection required trafficking to a low p ...200818829060
identification of the rem-responsive element of mouse mammary tumor virus.mouse mammary tumor virus (mmtv) has previously been shown to encode a functional homolog of the human immunodeficiency virus-1 (hiv-1) nuclear export protein rev, termed rem. here, we show that deletion of the rem gene from a mmtv molecular clone interfered with the nucleo-cytoplasmic transport of genomic length viral mrna and resulted in a loss of viral capsid (gag) protein production. interestingly, nuclear export of single-spliced env mrna was only moderately affected, suggesting that this t ...200818835854
rbpj conditional knockout reveals distinct functions of notch4/int3 in mammary gland development and tumorigenesis.transgenic mice expressing the notch 4 intracellular domain (icd) (int3) in the mammary gland have two phenotypes: arrest of mammary alveolar/lobular development and mammary tumorigenesis. notch4 signaling is mediated primarily through the interaction of int3 with the transcription repressor/activator rbpj. we have conditionally ablated the rbpj gene in the mammary glands of mice expressing whey acidic protein (wap)-int3. interestingly, rbpj knockout mice (wap-cre(+)/rbpj(-/-)/wap-int3) have nor ...200918836481
inability of human immunodeficiency virus type 1 produced in murine cells to selectively incorporate primer formula.attempts to use the mouse as a model system for studying aids are stymied by the multiple blocks to human immunodeficiency virus type 1 (hiv-1) replication that exist in mouse cells at the levels of viral entry, transcription, and gag assembly and processing. in this report, we describe an additional block in the selective packaging of trna(3lys) into hiv-1 produced in murine cells. hiv-1 and murine leukemia virus (mulv) use trna(3lys) and trna(pro), respectively, as primers for reverse transcri ...200818842718
balb/mtv-null mice responding to strong mouse mammary tumor virus superantigens restrict mammary tumorigenesis.the absence of endogenous mouse mammary tumor viruses (mmtvs) in the congenic mouse strain, balb/mtv-null, restricts the early steps of exogenous c3h mmtv infection, preventing the superantigen (sag) response and mammary tumorigenesis. here we demonstrate that balb/mtv-null mice also resist tumor induction by fm mmtv, which encodes a stronger sag compared to c3h mmtv. in contrast to infections with c3h mmtv, mtv-null mice show fm-mmtv sag-specific responses comparable to those observed in suscep ...200918922863
black cohosh increases metastatic mammary cancer in transgenic mice expressing c-erbb2.black cohosh is an herbal extract that is often used as an alternative to estrogen-based replacement therapies to treat hot flushes that frequently accompany the transition to menopause. although cancer-free women as well as breast cancer patients and survivors use black cohosh to relieve vasomotor symptoms, there is limited information on its potential to influence breast cancer development or progression. therefore, in this study, the effects of black cohosh on mammary tumorigenesis were inves ...200818922910
mammary tumors initiated by constitutive cdk2 activation contain an invasive basal-like component.the basal-like subtype of breast cancer is associated with invasiveness, high rates of postsurgical recurrence, and poor prognosis. aside from inactivation of the brca1 tumor-suppressor gene, little is known concerning the mechanisms that cause basal breast cancer or the mechanisms responsible for its invasiveness. here, we show that the heterogeneous mouse mammary tumor virus-cyclin d1-cdk2 (mmtv-d1k2) transgenic mouse mammary tumors contain regions of spindle-shaped cells expressing both lumin ...200818953433
regulation of cyclin d1 and wnt10b gene expression by camp-responsive element-binding protein during early adipogenesis involves differential promoter methylation.cyclin d1 expression is elevated and wnt10b is repressed by camp during the first few hours of adipogenesis. camp-responsive element-binding protein (creb) is a primary target for camp signaling, and we have shown that activation of creb promotes adipogenesis and adipocyte survival. here we tested the impact of creb on expression of cyclin d1 and wingless-related mouse mammary tumor virus integration site 10b (wnt10b) in 3t3-l1 cells. forced depletion of creb blocked bt(2)camp-stimulated cyclin ...200818957421
increased production of a secreted glycoprotein in engineered cho cells through amplification of a transcription factor.expression levels of reporter protein driven by mouse mammary tumor virus promoter system were improved by expressing its specific transcription factor (glucocorticoid receptor) from a different expression vector. the vector that expresses glucocorticoid receptor (gr) also contained dihydrofolate reductase (dhfr) gene as a selection marker. in the presentstudy we amplified the glucocorticoid receptor gene (gr)along with the dhfr gene by adapting the cell lines to increasing concentrations of met ...200219003083
long-term low level glucocorticoid exposure induces persistent repression in chromatin.environmental exposure to low concentration hormones can have permanent epigenetic effects in animals and humans. the consequence of long-term low concentration glucocorticoid exposure was investigated in cell culture using glucocorticoid responsive genes organized in alternative chromatin structures. the mmtv promoter is induced by short-term glucocorticoid exposure on either an integrated (normal chromatin) or transient (unstructured chromatin) promoter. longer hormone treatment causes a trans ...200919007849
a ras recruitment screen identifies zkscan4 as a glucocorticoid receptor-interacting protein.to search for proteins interacting with the glucocorticoid receptor, we adapted aronheim's reverse ras recruitment system relying on the saccharomyces cerevisiae mutant cdc25-2, which has a temperature-dependent defect in its ras signaling pathway driving proliferation. the full-length human glucocorticoid receptor (nr3c1, isoform-alpha) was attached to the yeast plasma membrane in either of two orientations and used as bait to screen a hela cell cdna library. library proteins were fused to cons ...200919008334
the possible involvement of virus in breast cancer.it is well known that the etiology of human breast cancer is significantly affected by environmental factors. virus-associated cancer refers to a cancer where viral infection results in the malignant transformation of the host's infected cells. human papillomaviruses (hpv), mouse mammary tumor virus (mmtv) and epstein-barr (ebv) virus are prime candidate viruses as agents of human breast cancer. the precise role that viruses play in tumorigenesis is not clear, but it seems that they are responsi ...200919009309
biotinylation of histones represses transposable elements in human and mouse cells and cell lines and in drosophila melanogaster.transposable elements such as long terminal repeats (ltr) constitute approximately 45% of the human genome; transposition events impair genome stability. fifty-four promoter-active retrotransposons have been identified in humans. epigenetic mechanisms are important for transcriptional repression of retrotransposons, preventing transposition events, and abnormal regulation of genes. here, we demonstrate that the covalent binding of the vitamin biotin to lysine-12 in histone h4 (h4k12bio) and lysi ...200819022951
in vivo mouse model for analysis of hydroxysteroid (17beta) dehydrogenase 1 inhibitors.hydroxysteroid (17beta) dehydrogenase 1 (hsd17b1) catalyzes the reaction between the low active 17-ketosteroids and the highly active 17beta-hydroxysteroids. in the present study, we have generated transgenic (tg) mice expressing human (h) hsd17b1 under mouse mammary tumor virus (mmtv) promoter (mmtv-hhsd17b1tg mice). the mmtv-hhsd17b1tg mice were used to characterize hsd17b1 enzyme activity and properties of hsd17b1 inhibitor in vivo. expression of the transgene was detected by enzyme activity ...200919026716
a composite intronic element directs dynamic binding of the progesterone receptor and gata-2.the progesterone receptor (pr) plays a pivotal role in proper development and function of the mammary gland and has also been implicated in mammary tumorigenesis. pr is a ligand-activated transcription factor; however, relatively, little is known about its mechanisms of action at endogenous target promoters. the aim of our study was to identify a natural pr-responsive gene and investigate its transcriptional regulation in the mammary microenvironment. our experiments revealed fkbp5 as a direct t ...200919036901
premature processing of mouse mammary tumor virus gag polyprotein impairs intracellular capsid assembly.mouse mammary tumor virus (mmtv) is the prototypical member of the betaretrovirus genus, but the processes of its morphogenesis are poorly characterized. in this report, we describe an unusual intracellular processing of mmtv gag polyprotein in human 293t cells transiently expressing mmtv from heterologous promoter. the same specific cleavage products of the viral protease were seen for the wild type as well as for nonmyristylated mutant of mmtv gag polyprotein completely defective in the partic ...200919046754
activation of phosphatidylinositol 3-kinase by membrane localization of p110alpha predisposes mammary glands to neoplastic transformation.phosphatidylinositol 3-kinases (pi3k) constitute important regulators of various signaling pathways with relevance in cancer. enhanced activation of p110alpha, the catalytic subunit of pi3k, was found in a high proportion of many human tumor types. we generated a mouse model in which pi3k is activated by forced recruitment of p110alpha to the membrane. different transgenic lines expressing myristoylated p110alpha protein under the control of the epithelial-specific mouse mammary tumor virus prom ...200819047141
increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy.pregnancy results in the transfer of stem cells from the fetus to the maternal circulation. these cells are able to migrate and differentiate within various damaged maternal tissues. we recently showed the presence of fetal-derived cells in human breast carcinomas during pregnancy. in this study, we aimed to reproduce these results in a murine model of "pregnancy-associated" breast carcinoma. we bred virgin mmtv-h-ras transgenic female mice with male mice transgenic for luciferase under the cont ...200919065666
interferons and progesterone for establishment and maintenance of pregnancy: interactions among novel cell signaling pathways.type i and/or type ii interferons (ifns) are important in establishing uterine receptivity to implantation in mammals. gene expression effected by ifns may be induced, stimulated or inhibited, but most are ifn-stimulated genes (isgs). effects of ifns range from pregnancy recognition signaling in ruminants by ifn tau (ifnt) to effects on cellular functions of the uterus and uterine vasculature. for most, if not all, actions of ifns on the uterus, progesterone (p(4)) is permissive to isg expressio ...200819092983
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