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can mmtv exploit tlr4?the recognition of microbial pathogens based on their molecular patterns is essential for host defense. recently, toll-like receptors have been shown not only to recognize viruses as well as bacteria and fungi, but also to trigger an efficient immune response. a recent publication proposed that the retrovirus mouse mammary tumor virus exploits the pattern-recognition receptor toll-like receptor 4 to achieve more efficient infection.200212110201
trans-activation and repression properties of the novel nonsteroid glucocorticoid receptor ligand 2,5-dihydro-9-hydroxy-10-methoxy-2,2,4-trimethyl-5-(1-methylcyclohexen-3-y1)-1h-[1]benzopyrano[3,4-f]quinoline (a276575) and its four stereoisomers.glucocorticoids are potent anti-inflammatory and immunosuppressant agents. however, they also produce serious side effects that limit their usage. it has been proposed that anti-inflammatory properties of glucocorticoids are caused mostly by repression of activator protein 1- and nuclear factor kappabeta-stimulated synthesis of inflammatory mediators, whereas most of their adverse effects are associated with trans-activation of genes involved with metabolic processes. our laboratories have sough ...200212130681
inducible expression of fgf-3 in mouse mammary gland.fibroblast growth factor-3 (fgf-3) is a crucial developmental regulator. aberrant activation of this gene by mouse mammary tumor virus insertion results in pregnancy-responsive mammary tumorigenesis. to characterize better fgf-3 function in postnatal mammary gland development and cancer initiation/progression, we used a mifepristone (ru486)-inducible regulatory system to express conditionally fgf-3 in the mammary epithelium of transgenic mice. ectopic overexpression of fgf-3 in pubescent mammary ...200212169667
[effect of 5-azacytidine on expression of dna sequences homologous to env gene of murine mammary tumor virus in normal human lymphocytes].expression of dna sequences, related to mmtv env gene, in peripheral blood lymphocytes, which was strictly specific for human mammary carcinoma, has been previously reported. these sequences (homologous to env gene site coding for mmtv gp52 envelope antigen) expressed in t cells can play the key role in virus infection transmission and propagation. in order to elucidate the possible routes of env mmtv-homologous sequences expression, we tried to induced it in donot t lymphocytes by various metho ...200212180024
tef-1 transcription factors regulate activity of the mouse mammary tumor virus ltr.the mouse mammary tumor virus long terminal repeat (ltr) is a potent transcriptional enhancer. we identified several putative binding sites for the tef-1 family of transcription factors (tef-1, rtef-1, dtef-1, and etf) in the proximal negative regulatory element of the ltr. gel mobility shift assays revealed strong tef-1 factor binding to one site using nuclear extracts from cv-1 cells and from the human breast cancer cell line mcf-7. mutation of this site increased basal activity of the ltr. in ...200212207913
human breast cancer and lymphomas may share a common aetiology involving mouse mammary tumour virus (mmtv).mouse mammary tumour virus (mmtv) causes breast tumours in mice, and has been implicated in the aetiology of murine lymphomas. several recent human studies have detected mmtv-env dna sequences in 30-40% of tumours from breast cancer patients but in less than 4% of normal breast tissue. mmtv dna has been detected in simultaneously diagnosed primary lymphoma and breast cancer tissue, suggesting mmtv may be involved in the aetiology of both breast cancer and lymphoma. we further hypothesize that if ...200212208195
characterization of deoxyuridine 5'-triphosphate nucleotidohydrolase from trypanosoma cruzi.we report the cloning and kinetic characterization of trypanosoma cruzi deoxyuridine 5'-triphosphate nucleotidohydrolase (dutpase) whose coding sequence was isolated by genetic complementation in escherichia coli. the deduced amino acid sequence was similar to leishmania major dutpase although it exhibits an amino acid insertion which is sensitive to protease inactivation. the catalytically active species of the enzyme is a dimer and a detailed kinetic characterization showed that it is highly s ...200212208522
human immunodeficiency virus type 1 (hiv-1) accessory protein vpr induces transcription of the hiv-1 and glucocorticoid-responsive promoters by binding directly to p300/cbp coactivators.the accessory vpr protein of human immunodeficiency virus type 1 (hiv-1) is a promiscuous activator of viral and cellular promoters. we report that vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (mmtv) promoter and of the tat-induced hiv-1 long terminal repeat promoter by directly binding to p300/cbp coactivators. in contrast, vpr does not bind to p/caf or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivato ...200212208951
conditional over-expression of estrogen receptor alpha in a transgenic mouse model.attempts to delineate the mechanisms of estrogen action have promoted the creation of several estrogen receptor alpha (eralpha) mouse models in the past decade. these traditional models are limited by the fact that the receptors are either absent or present throughout all stages of development. the purpose of this work was to develop a conditional transgenic model that would provide an in vivo method of controlling the spatial and temporal regulation of eralpha expression. the tetracycline respo ...200212212839
glucocorticoids modulate transformation by v-src in a cell-specific manner.in balb 3t3 murine fibroblasts infected with retroviruses carrying the v-src oncogene, treatment with the glucocorticoid hormone dexamethasone induces a 10-fold increase in the number of transformed foci and of anchorage-independent colonies. in contrast, in nih-3t3-infected cells the number of foci and of colonies growing in soft agar is considerably reduced by the addition of the hormone. the effect of dexamethasone on both balb 3t3 and nih 3t3 cells is dose-dependent and mediated by specific ...200212213218
mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus.enveloped viruses enter cells by binding to their entry receptors and fusing with the membrane at the cell surface or after trafficking through acidic endosomal compartments. species-specific virus tropism is usually determined by these entry receptors. because mouse mammary tumor virus (mmtv) is unable to infect chinese hamster cells, we used phenotypic screening of the t31 mouse/hamster radiation hybrid panel to map the mmtv cell entry receptor gene and subsequently found that it is transferri ...200212218182
weight-cycling decreases incidence and increases latency of mammary tumors to a greater extent than does chronic caloric restriction in mouse mammary tumor virus-transforming growth factor-alpha female mice.multiple periods of caloric restriction (or fasting)/refeeding in rodents have had inconsistent effects on mammary tumor (mt) development. in the present study, the consequence of intermittent caloric restriction/refeeding resulting in weight-cycling was evaluated using an oncogene-induced mt mouse model. hybrid mouse mt virus-transforming growth factor alpha (mmtv-tgf-alpha)/lep(+)lep(ob) female mice were used. ad libitum-fed mice (n = 30) were fed american institute of nutrition (ain)-93m diet ...200212223427
[the possibility of the retroviruses participation in human breast neoplasm induction].the existence of retrovirus related to murine mammary tumor virus (mmtv) and specifically associated with mammary carcinoma has been suggested long ago. this review covers some papers published in the 70-80ies until now, containing evidence for this suggestion. in spite of a lack of direct proof of virus existence this problem still remains to be solved. there are some indications that both in man and in mice, peripheral blood lymphocytes participate in the circulation of the supposed viral agen ...200212271725
[detection of murine mammary tumor virus (mmtv) env gene-like sequences in breast cancer from argentine patients].in the last years research on the possible viral etiology of human breast cancer has been revised. previous studies have demonstrated the presence of a mouse mammary tumor virus (mmtv) env gene-like sequence in about 38% of breast cancers from american and italian women; these sequences are generally absent in other tumors and in normal mammary tissue. in the present study we have analyzed the presence of a 250-bp sequence of the mmtv env gene in breast cancer biopsies from argentine patients. t ...200212325488
origin and progression of pregnancy-dependent mammary tumors induced by new mouse mammary tumor virus variants.in order to study mechanisms of progression of mouse mammary tumor virus (mmtv)-induced pregnancy-dependent mammary lesions, we removed and serially transplanted 17 small tumors detected in mmtv-infected pregnant females. this gave rise to the same number of 'in vivo' tumor lines. hormone-dependency of the passages was determined by comparing tumor development in multiparous versus virgin hosts. we found that the first passages of most of these lesions (11/17) required pregnancy to grow. however ...200212353808
celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (her-2)/neu-induced breast cancer.cyclooxygenase 2 (her-2) (cox-2), an inducible form of cox, is overexpressed in her-2/neu-positive human breast cancers. the aim of this study was to determine whether celecoxib, a selective cox-2 inhibitor, protected against her-2/neu-induced experimental breast cancer. cox-2 protein was detected in breast carcinomas from mouse mammary tumor virus (mmtv)/neu mice. treatment with celecoxib (500 ppm) significantly reduced the incidence of mammary tumors in mmtv/neu mice (p = 0.003) and caused abo ...200212359744
matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo.overexpression of the matrix metalloproteinase matrilysin (matrix metalloproteinase-7) in the mouse mammary gland promotes mammary hyperplasia and accelerates the onset of oncogene-induced mammary tumors. in cell culture models, acute exposure of cells coexpressing fas and fas ligand (fasl) to matrilysin induces apoptosis, whereas chronic exposure to matrilysin selects for apoptosis-resistant cells. we now demonstrate that matrilysin promotes resistance to apoptosis in vivo. matrilysin expressio ...200212359768
differential activation of the ikappabalpha and mouse mammary tumor virus promoters by progesterone and glucocorticoid receptors.the glucocorticoid and progesterone receptors (gr and pr) are structurally homologous and bind a common hormone response element (hre). the mechanisms by which receptors activate specific promoters when multiple steroids are present in a cell is a critical question in endocrinology. to investigate how co-existing steroid receptors regulate gene transcription, we have compared two hormone-responsive promoters in t47d/a1-2 human breast cancer cells expressing both the gr and pr. the promoters chos ...200212361720
regions of mouse mammary tumor virus superantigen involved in interaction with the major histocompatibility complex class ii i-a molecule.to study the major histocompatibility complex class ii i-e dependence of mouse mammary tumor virus (mmtv) superantigens, we constructed hybrids between the i-e-dependent mmtv(gr) and the i-e-independent mtv-7 superantigens and tested them in vivo. our results suggest that, although the c-terminal third mediates i-a interaction, additional binding sites are located elsewhere in the superantigen.200212368363
soy isoflavones increase latency of spontaneous mammary tumors in mice.soy protein, with and without isoflavones, is being added to foods by manufacturers in response to the food and drug administration (fda)-approved health claim for cardiovascular protection. furthermore, soy isoflavones are increasingly consumed by women in the united states as an alternative to hormone replacement therapy. the role of these phytoestrogens in breast cancer is controversial. although exposure of rodents to soy isoflavones during the perinatal period appears to reduce mammary canc ...200212368416
antagonism of glucocorticoid receptor transactivity and cell growth inhibition by transforming growth factor-beta through ap-1-mediated transcriptional repression.we have examined the interaction of the glucocorticoid receptor (gr) and transforming growth factor-beta (tgf-beta) signal pathways because of their mutual involvement in the regulation of cell growth, development and differentiation. most studies of this cross-talk event have focused on the effects of glucocorticoids (gcs) on tgf-beta responses. in this work, we show that tgf-beta can antagonize dexamethasone (dex)-mediated growth suppression in mouse fibrosarcoma l929 cells. tgf-beta also repr ...200212379279
perturbation of beta1-integrin function in involuting mammary gland results in premature dedifferentiation of secretory epithelial cells.to study the mechanism of beta1-integrin function in vivo, we have generated transgenic mouse expressing a dominant negative mutant of beta1-integrin under the control of mouse mammary tumor virus (mmtv) promoter (mmtv-beta1-cyto). mammary glands from mmtv-beta1-cyto transgenic females present significant growth defects during pregnancy and lactation and impaired differentiation of secretory epithelial cells at the onset of lactation. we report herein that perturbation of beta1-integrin function ...200212388754
mouse mammary tumor-like env gene as a molecular marker for breast cancer? 200212397656
chlorpromazine inhibits the glucocorticoid receptor-mediated gene transcription in a calcium-dependent manner.antipsychotic drugs can modulate transcription factors and also nuclear receptors, but their action on glucocorticoid receptors (gr)-members of the steroid/thyroid hormone receptor family has not been studied so far. in the present study we investigated effects of various antipsychotics on the glucocorticoid-mediated gene transcription in fibroblast cells, stably transfected with a mouse mammary tumor virus promoter (lmcat cells). chlorpromazine (3-100 microm) inhibited the corticosterone-induce ...200212423673
mammary stem cell repertoire: new insights in aging epithelial populations.the proliferative lifespan of mammary stem cells was examined in serially transplanted clonal-dominant epithelial populations. five successive transplant generations were done. the epithelial cell number in each outgrowth expands approximately 500-fold in nulliparous hosts and approximately 10000-fold in impregnated hosts. despite this, all resulting mammary outgrowths showed lineal identity with the original. growth senescence was observed in some implants beginning at the third generation in i ...200212425957
initiation site binding protein and the initiator-like promoter element of mouse mammary tumor virus.the mouse mammary tumor virus (mmtv) promoter contains an element near its transcription initiation site that is recognized by a protein termed initiation site binding protein (isbp). spacing between the tata box and the isbp site is important for mmtv promoter function, as altered spacing results in heterogeneity in start site selection in vitro and in vivo. the sequence of the isbp site is related to initiator elements common in many rna polymerase ii promoters. however, binding of partially p ...200212429527
wnt and fgf gene clusters (review).mouse mammary tumor virus (mmtv) is a retrovirus, activating wnt genes (wnt1/int-1, wnt3/int-4, wnt10b), fgf genes (fgf3/int-2, fgf4, fgf8) and other genes (notch4/int-3, eif3s6/int-6) due to proviral integration. among 19 wnt genes, wnt3 and wnt14b genes are clustered in human chromosome 17q21, wnt3a and wnt14 in human chromosome 1q42, wnt10a and wnt6 in human chromosome 2q35, and wnt10b and wnt1 in human chromosome 12q13. among 22 fgf genes, fgf19, fgf4 and fgf3 genes are clustered in human ch ...200212429977
expression of a truncated brca1 protein delays lactational mammary development in transgenic mice.to address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene brca1 have biological activity in vivo, we have expressed a truncated brca1 protein (trbrca1) in cell-lines and in the mammary gland of transgenic mice. immunofluorescent analysis of transfected cell-lines indicates that trbrca1 is a stable protein and that it is localized in the cell cytoplasm. functional analysis of these cell-lines indicates that expression of trbrca1 confers an ...200212437078
the retinoid x receptor-selective retinoid, lgd1069, prevents the development of estrogen receptor-negative mammary tumors in transgenic mice.despite the effectiveness of the selective estrogen receptor (er) modulators in preventing er-positive breast cancer, chemopreventive agents still need to be developed for the prevention of er-negative breast cancers. the naturally occurring retinoids are promising agents for the prevention of human cancers but are too toxic for long-term chronic use. we previously demonstrated that the chemopreventive effects of the retinoids could be separated from the toxicity by using an rxr-selective retino ...200212438218
protein kinase ck2 promotes aberrant activation of nuclear factor-kappab, transformed phenotype, and survival of breast cancer cells.the her-2/neu oncogene, the second member of the epidermal growth factor (egf) receptor family, encodes a transmembrane tyrosine kinase receptor. overexpression of her-2/neu in approximately 30% of breast cancers is associated with poor overall survival. recently, we have found that her-2/neu activates nuclear factor (nf)-kappab via a phosphatidylinositol 3 kinase (pi3-k)-akt kinase signaling pathway in mouse mammary tumor virus (mmtv)-her-2/neu nf639 mouse breast cancer cells. surprisingly, the ...200212438279
asymmetric binding of histone h1 stabilizes mmtv nucleosomes and the interaction of progesterone receptor with the exposed hre.packaging of mouse mammary tumor virus (mmtv) promoter sequences in nucleosomes modulates access of dna binding proteins and influences the interaction among dna bound transcription factors. here we analyze the binding of histone h1 to mmtv mononucleosomes assembled with recombinant histones and study its influence on nucleosome structure and stability as well as on progesterone receptor (pr) binding to the hormone responsive elements (hres). the mmtv nucleosomes can be separated into three main ...200212445785
dynamic behavior of transcription factors on a natural promoter in living cells.through the use of photobleaching techniques, we examined the dynamic interaction of three members of the transcription apparatus with a target promoter in living cells. the glucocorticoid receptor (gr) interacting protein 1 (grip-1) exhibits a half maximal time for fluorescent recovery (tau(r)) of 5 s, reflecting the same rapid exchange as observed for gr. in contrast, the large subunit (rpb1) of rna polymerase ii (pol ii) required 13 min for complete fluorescence recovery, consistent with its ...200212446572
heparin-binding epidermal growth factor-like growth factor stimulates androgen-independent prostate tumor growth and antagonizes androgen receptor function.peptide growth factors have been implicated in progression of prostate cancer (pca) to the androgen-independent state; however, much of the evidence linking diffusible mitogens and survival factors to this process remains circumstantial. heparin-binding epidermal growth factor-like growth factor (hb-egf), a prostate stroma-derived factor, promotes survival, proliferation, and neuroendocrine differentiation of androgen-dependent lncap pca cells in vitro. to test whether sustained exposure to hb-e ...200212446587
attenuation of glucocorticoid signaling through targeted degradation of p300 via the 26s proteasome pathway.the effects of acetylation on gene expression are complex, with changes in chromatin accessibility intermingled with direct effects on transcriptional regulators. for the nuclear receptors, both positive and negative effects of acetylation on specific gene transcription have been observed. we report that p300 and steroid receptor coactivator 1 interact transiently with the glucocorticoid receptor and that the acetyltransferase activity of p300 makes an important contribution to glucocorticoid re ...200212456802
genes involved in breast cancer progression: analysis of global changes in gene expression or retroviral tagging? 200212466111
acceleration of mouse mammary tumor virus-induced murine mammary tumorigenesis by a p53 172h transgene: influence of fvb background on tumor latency and identification of novel sites of proviral insertion.we previously showed that a mammary-specific dominant-negative p53 transgene (wap-p53(172h)) could accelerate erbb2-induced mammary tumorigenesis in mice, but was not tumorigenic on its own. to identify other genes that cooperate with wap-p53(172h) in tumorigenesis, we performed mouse mammary tumor virus (mmtv) proviral mutagenesis. we derived f1, n2, and n4/n5 mice from p53(172h) transgenic fvb mice backcrossed onto mmtv+ c3h/he mice. results show the latency of mmtv tumorigenesis is correlated ...200212466138
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
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
reduced expression of int-6/eif3-p48 in human tumors.the int-6 gene, originally identified as a common integration site for the mouse mammary tumor virus (mmtv) in mouse mammary tumors, encodes the p48 component of the eukaryotic translation initiation factor-3 (eif3-p48). int-6/eif3-p48 is expressed in all adult tissues which have been tested and early in embryonic development. int-6/eif3-p48 has been highly conserved throughout evolution and the deduced amino acid sequence of the human gene product is identical to the mouse protein. viral insert ...200111115556
fission yeast homolog of murine int-6 protein, encoded by mouse mammary tumor virus integration site, is associated with the conserved core subunits of eukaryotic translation initiation factor 3.the murine int-6 locus, identified as a frequent integration site of mouse mammary tumor viruses, encodes the 48-kda eif3e subunit of translation initiation factor eif3. previous studies indicated that the catalytically active core of budding yeast eif3 consists of five subunits, all conserved in eukaryotes, but does not contain a protein closely related to eif3e/int-6. whereas the budding yeast genome does not encode a protein closely related to murine int-6, fission yeast does encode an int-6 ...200111134033
evaluation of in vitro methods for detecting the effects of various chemicals on the human progesterone receptor, with a focus on pyrethroid insecticides.the progesterone receptor (pr) is associated with physiological events such as implantation and the maintenance of pregnancy. recently, it has become a social concern that chemicals may exert agonistic or antagonistic effects on hormone receptors. therefore, we examined the effects of various chemicals on the human pr, with a focus on pyrethroid insecticides, using three in vitro methods. eight pyrethroid insecticides (fenvalerate, d-allethrin, d-phenothrin, prallethrin, empenthrin, permethrin, ...200111137321
c-myc induces mammary tumorigenesis by means of a preferred pathway involving spontaneous kras2 mutations.although the process of mammary tumorigenesis requires multiple genetic events, it is unclear to what extent carcinogenesis proceeds through preferred secondary pathways following a specific initiating oncogenic event. similarly, the extent to which established mammary tumors remain dependent on individual mutations for maintenance of the transformed state is unknown. here we use the tetracycline regulatory system to conditionally express the human c-myc oncogene in the mammary epithelium of tra ...200111175856
green tea polyphenols as potent enhancers of glucocorticoid-induced mouse mammary tumor virus gene expression.the effect of natural and synthetic galloyl esters on glucocorticoid-induced gene expression was evaluated by using rat fibroblast 3y1 cells stably transfected with a luciferase reporter gene under the transcriptional regulation of the mouse mammary tumor virus promoter. the glucocorticoid-induced gene transcription was strongly suppressed by synthetic alkyl esters; n-dodecyl gallate showed the most potent inhibition (66% inhibition at 10 microm), which was far more potent than that of crude tan ...200111178969
normal pathogen-specific immune responses mounted by ctla-4-deficient t cells: a paradigm reconsidered.ctla-4 is a critical negative regulator of t cell responses and ctla-4-deficient (ctla-4(-/-)) mice die of a lymphproliferative disease. nevertheless, rag-2-deficient mice reconstituted with a mixture of ctla-4(-/-) and normal (ctla-4(+/+)) bone marrow survive in the absence of any signs of disease, although 50% of their t cells do not express ctla-4. using such mixed chimeras, we analyzed the role of ctla-4 in specific t cell responses to lymphocytic choriomeningitis virus, leishmania major and ...200111180109
changing responsiveness to chemokines allows medullary plasmablasts to leave lymph nodes.during t cell-dependent antibody responses lymph node b cells differentiate either to plasmablasts that grow in the medullary cords, or to blasts that proliferate in follicles forming germinal centers. many plasmablasts differentiate to plasma cells locally, but some leave the medullary cords and migrate to downstream lymph nodes. to assess the basis for this migration, changes in the responsiveness of b cells to a range of chemokines have been studied as they differentiate. naive b cells expres ...200111180126
cloning and in vitro characterization of alpha 1(i)-collagen 11 beta-hydroxysteroid dehydrogenase type 2 transgenes as models for osteoblast-selective inactivation of natural glucocorticoids.the nad-dependent enzyme, 11beta-hydroxysteroid dehydrogenase type ii (11 beta hsd2), catalyzes the unidirectional conversion of biologically active glucocorticoids to inactive metabolites. in vivo, 11 beta hsd2 protects the mineralocorticoid receptor from activation by glucocorticoids in mineralocorticoid target tissues such as kidney. the goal of the present study was to use targeted overexpression of 11 beta hsd2 as a novel means of disrupting glucocorticoid signaling in osteoblastic cells. r ...200111181553
role of promyelocytic leukemia (pml) protein in tumor suppression.the promyelocytic leukemia (pml) gene encodes a putative tumor suppressor gene involved in the control of apoptosis, which is fused to the retinoic acid receptor alpha (raralpha) gene in the vast majority of acute promyelocytic leukemia (apl) patients as a consequence of chromosomal translocations. the pmlraralpha oncoprotein is thought to antagonize the function of pml through its ability to heterodimerize with and delocalize pml from the nuclear body. in apl, this may be facilitated by the red ...200111181703
association of mouse mammary tumor virus superantigen with mhc class ii during biosynthesis.mouse mammary tumor viruses encode superantigens that interact with mhc class ii proteins and stimulate t cells. we show here that presentation of mouse mammary tumor virus superantigen does not require dm. furthermore, we have identified a strong class ii peptide binding motif in the mtv-7 superantigen, and we show that this motif is necessary for association with class ii molecules in in vitro translation and in vivo functional assays. our results suggest that endogenously synthesized viral su ...200111207286
overexpression of membrane-type matrix metalloproteinase-1 gene induces mammary gland abnormalities and adenocarcinoma in transgenic mice.to investigate the role of membrane-type matrix metalloproteinase-1 (mt1-mmp) in mammary gland development and tumorigenesis, transgenic mice overexpressing mt1-mmp in mammary gland under the control of the mouse mammary tumor virus long terminal repeat-promoter were generated. the mouse mammary tumor virus/mt1-mmp transgenic mice displayed abnormalities in 82% of female mammary glands. the abnormalities were verified as lymphocytic infiltration, fibrosis, hyperplasia, alveolar structure disrupt ...200111221894
search for mouse mammary tumor virus-like env sequences in cancer and normal breast from the same individuals.we have reported previously that a 660-bp sequence homologous to the env gene of the mouse mammary tumor virus, but not to the known endogenous retroviruses, was present in 38% of human breast cancers (y. wang et al., cancer res., 55: 5173-5179, 1995). a unique 250-bp internal sequence was equally present in formalin-fixed breast carcinoma. it was not detected in normal human breasts or in other tumors. in this study, we have investigated whether this 250-bp env sequence was also present in the ...200111234880
diverse repertoire of the mhc class ii-peptide complexes is required for presentation of viral superantigens.among other features, peptides affect mhc class ii molecules, causing changes in the binding of bacterial superantigens (b-sag). whether peptides can alter binding of viral superantigens (v-sag) to mhc class ii was not known. here we addressed the question of whether mutations limiting the diversity of peptides bound by the mhc class ii molecules influenced the presentation of v-sag and, subsequently, the life cycle of the mouse mammary tumor virus (mmtv). t cells reactive to v-sag were found in ...200111160278
type b leukemogenic virus has a t-cell-specific enhancer that binds aml-1.type b leukemogenic virus (tblv) induces rapidly appearing t-cell tumors in mice. tblv is highly related to mouse mammary tumor virus (mmtv) except that tblv long terminal repeats (ltrs) have a deletion of negative regulatory elements and a triplication of sequences flanking the deletion. to determine if the ltr triplication represents a viral enhancer element, we inserted the triplication upstream and downstream in either orientation relative to the thymidine kinase promoter linked to the lucif ...200111160721
activation of akt (protein kinase b) in mammary epithelium provides a critical cell survival signal required for tumor progression.activation of akt by the phosphatidylinositol 3'-oh kinase (pi3k) results in the inhibition of proapoptotic signals and the promotion of survival signals (l. p. kane et al., curr. biol. 9:601-604, 1999; g. j. kops et al., nature 398:630-634, 1999). evidence supporting the importance of the pi3k/akt signaling pathway in tumorigenesis stems from experiments with transgenic mice bearing polyomavirus middle t antigen under the control of the mouse mammary tumor virus long terminal repeat promoter. m ...200111238953
identification of a proviral structure in human breast cancer.involvement of a virus similar to mouse mammary tumor virus (mmtv) in human breast cancer has long been postulated but never demonstrated. we have detected by pcr a 660-bp sequence similar to the env gene of mmtv but not to the known endogenous viruses, in 38% of human breast cancers examined (wang et al., cancer res., 55: 5173-5179, 1995). this sequence was expressed in 66% of the env-positive tumors as detected by reverse transcription-pcr (wang et al., clin. cancer res., 4: 2565-2568, 1998). ...200111245493
up-regulation of muc1 in mammary tumors generated in a double-transgenic mouse expressing human muc1 cdna, under the control of 1.4-kb 5' muc1 promoter sequence and the middle t oncogene, expressed from the mmtv promoter.in this study we examined the regulation of expression of the human muc1 gene in vivo, by developing muc1 transgenic mice. the data showed that epithelial-specific expression of muc1 can be directed by just 1.4 kb of 5' flanking sequence using muc1 cdna as a reporter gene in vivo. furthermore, high levels of muc1 expression were seen in the lactating mammary gland and in spontaneous mammary tumors generated by crossing the muc1 transgenics with mice transgenic for the polyoma middle t oncogene u ...200111291075
detection of mmtv-like ltr and ltr-env gene sequences in human breast cancer.we have previously reported, using the polymerase chain reaction (pcr), the presence of a 660 bp sequence homologous to the env gene of mmtv in 38% of the human breast cancers studied, but not in normal breasts nor in other tumors or tissues. we have now investigated the presence of mmtv-like ltr sequences in human breast cancer and normal breast tissue. primers were selected to amplify a 630 bp sequence homologous to mmtv, but not to the endogenous retrovirus herv-k10. this sequence was detecte ...200111295054
functional plasticity of the lack-reactive vbeta4-valpha8 cd4(+) t cells normally producing the early il-4 instructing th2 cell development and susceptibility to leishmania major in balb / c mice.early production of il-4 by lack-reactive vbeta4-valpha8 cd4(+) t cells instructs aberrant th2 cell development and susceptibility to leishmania major in balb / c mice. this was demonstrated using vbeta4(+)-deficient balb / c mice as a result of chronic infection with mmtv (sim), a mouse mammary tumor virus expressing a vbeta4-specific superantigen. the early il-4 response was absent in these mice which develop a th1 response to l. major. here, we studied the functional plasticity of lack-reacti ...200111298356
glucocorticoid hormone-induced receptor localization to the chromatin fibers formed on injected dna in xenopus oocytes.oocytes from xenopus laevis have provided a model system for studying the dynamic changes that occur in chromatin during gene activation. we have reconstituted glucocorticoid receptor (gr) induced transcription from the mouse mammary tumor virus (mmtv) promoter by intranuclear injection of an mmtv-driven reporter and cytoplasmic injection of synthetic mrna(gr) into xenopus oocytes. here we investigate the intranuclear distribution of injected dna, which is assembled into chromatin. we show that ...200111302698
impairment of mammary lobular development induced by expression of tgfbeta1 under the control of wap promoter does not suppress tumorigenesis in mmtv-infected transgenic mice.it has previously been shown that transgenic female mice expressing tgfbeta1 under control of regulatory elements of the whey-acidic protein (wap) gene were unable to lactate. this was due to the increased apoptosis of the cells committed to the lobular-lactogenic phenotype. our goal was to determine whether the expression of wap-tgfbeta1 transgene could inhibit mmtv (mouse mammary tumor virus) tumorigenic activity in the mammary gland. it is well known that the infection with this virus produce ...200111304693
meta-controlled env-initiated transcripts encoding superantigens of murine mtv29 and mtv7 and their possible role in b cell lymphomagenesis.spontaneous germinal center (gc)-derived b cell lymphomas of sjl mice (rcs) transcribe a 1.8-kb mtv-29 mrna under control of the meta-env promoter. the encoded vsag29 stimulates syngeneic vbeta16(+) cd4(+) t cells, thereby acquiring t cell help necessary for rcs growth. other strains of b cell lymphoma-prone mice include mtv29(+) c57l and ma/myj, and the mtv29(-) mtv7(+)-recombinant inbred strain, sw x j-1. the lymphomas of these mice produce similar mouse mtv-vsag-encoding mrna, as characterize ...200111313379
inhibition of mammary epithelial apoptosis and sustained phosphorylation of akt/pkb in mmtv-igf-ii transgenic mice.igf-ii is a growth factor implicated in human cancers and animal tumor models. while the mitogenic properties of igf-ii are well documented, its ability to suppress apoptosis in vivo has never been proven. we generated independent mmtv-igf-ii transgenic mice to examine the control of epithelial apoptosis at the morphological, cellular and molecular levels during the physiological event of postlactation mammary involution. transgenic igf-ii expression was achieved in mammary epithelium and increa ...200111313699
abnormal ornithine decarboxylase activity in transgenic mice increases tumor formation and infertility.a transgenic mouse line carrying ornithine decarboxylase cdna as the transgene under the control of a mouse mammary tumor virus long terminal repeat (mmtv ltr) promoter was generated in order to study whether ornithine decarboxylase transgene expression will have any physiological or pathological effect during the entire life of a transgenic mouse. the high frequency of infertile animals and the loss of pups made the breeding of homozygous mice unsuccessful. however, a colony of heterozygous tra ...200111331206
delta n89 beta-catenin induces precocious development, differentiation, and neoplasia in mammary gland.to investigate the role of beta-catenin in mammary gland development and neoplasia, we expressed a stabilized, transcriptionally active form of beta-catenin lacking the nh(2)-terminal 89 amino acids (delta n 89 beta-catenin) under the control of the mouse mammary tumor virus long terminal repeat. our results show that delta n 89 beta-catenin induces precocious lobuloalveolar development and differentiation in the mammary glands of both male and female mice. virgin delta n 89 beta-catenin mammary ...200111331306
requirement for a complex array of costimulators in the negative selection of autoreactive thymocytes in vivo.autoreactive thymocytes can be deleted at an immature stage of their development by ag-induced apoptosis or negative selection. in addition to ag, negative selection also requires costimulatory signals from apc. we recently used a fetal thymus organ culture system to show that cd5, cd28, and tnf cooperatively regulate deletion of autoreactive thymocytes. although these experiments provided strong evidence for the action of several costimulators in negative selection, we wished to demonstrate a r ...200111342622
extrafollicular plasmablast b cells play a key role in carrying retroviral infection to peripheral organs.b cells can either differentiate in germinal centers or in extrafollicular compartments of secondary lymphoid organs. here we show the migration properties of b cells after differentiation in murine peripheral lymph node infected with mouse mammary tumor virus. naive b cells become activated, infected, and carry integrated retroviral dna sequences. after production of a retroviral superantigen, the infected b cells receive cognate t cell help and differentiate along the two main differentiation ...200111342650
superantigens: the good, the bad, and the ugly.increasing evidence suggests that superantigens play a role in immune-mediated diseases. superantigens are potent activators of cd4+ t cells, causing rapid and massive proliferation of cells and cytokine production. this characteristic of superantigens can be exploited in diseases where strong immunologic responses are required, such as in the b16f10 animal model of melanoma. superantigen administration is able to significantly enhance ineffective anti-tumor immune responses, resulting in potent ...200111361034
mammary gland involution is delayed by activated akt in transgenic mice.activation of the antiapoptotic protein kinase akt is induced by a number of growth factors that regulate mammary gland development. akt is expressed during mammary gland development, and expression decreases at the onset of involution. to address akt actions in mammary gland development, transgenic mice were generated expressing constitutively active akt in the mammary gland under the control of the mouse mammary tumor virus (mmtv) promoter. analysis of mammary glands from these mice reveals a ...200111376107
hormone-induced nucleosome positioning in the mmtv promoter is reversible.the mouse mammary tumor virus (mmtv) promoter is induced by glucocorticoid hormone via the glucocorticoid receptor (gr). the hormone-triggered effects on mmtv transcription and chromatin structure were studied in xenopus oocytes. we previously showed that the nucleosomes organizing the mmtv promoter became translationally positioned upon hormone induction. a single gr-binding site was necessary and sufficient for the chromatin events to occur, while transcription and basal promoter elements were ...200111387213
prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by dna vaccination.the her-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. the oncogenic potential of her-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. to test the efficacy of immune-based strategies in eliciting an antitumor response, we used the n#202 transgenic mouse model engineered to overexpress t ...200111402305
reducing mammary cancer risk through premature stem cell senescence.the reproductive capacity of the mammary epithelial stem cell is reduced coincident with the number of symmetric divisions it must perform. in a study of fvb/n mice with the transgene, wap-tgfbeta1, we discovered that mammary epithelial stem cells were prematurely aged due to ectopic expression of tgf-beta1. to test whether premature aging of mammary epithelial stem cells would have an impact on susceptibility or resistance to mammary cancer, female littermates from fvb/n x wap-tgf-beta1 mating ...200111402321
transactivation of murine cyclin a by polyomavirus large and small t antigens.polyomavirus large and small t antigens cooperate in the induction of s phase in serum-deprived swiss 3t3 cells. while the large t antigen is able to induce s phase-specific enzymes, we have recently shown that both t antigens contribute to the production of the cyclins e and a and that the small t antigen is essential for the induction of cyclin a-dependent cdk2 activity (s. schüchner and e. wintersberger, j. virol. 73:9266-9273, 1999). here we present our attempts to elucidate the mechanisms b ...200111413317
molecular cloning and characterization of wnt3a and wnt14 clustered in human chromosome 1q42 region.human wnt3a and wnt14 cdnas were cloned and characterized. wnt3a and wnt14 encoded wnt family protein of 352 and 365 amino acids, respectively. the 3.0-kb wnt3a mrna was moderately expressed in placenta, and the 4.4-kb wnt14 mrna was moderately expressed in skeletal muscle and heart. although wnt3a mrna was not detected in 35 human cancer cell lines, wnt14 mrna was expressed in gastric cancer cell lines tmk1, mkn7, mkn45 and kato-iii. wnt3a and wnt14 genes, clustered in the head to head manner w ...200111414706
cooperating oncogenic events in murine mammary tumorigenesis: assessment of erbb2, mutant p53, and mouse mammary tumor virus.we are investigating cooperating genetic events in the genesis of breast cancer, using the mouse as a model system. we have shown cooperativity between a mutant allele of p53 (p53-172h) and overexpressed erbb2 in mammary tumorigenesis in transgenic mice. we are now performing additional crosses to further examine oncogene cooperativity with erbb2 and p53-172h. we attempted to test the dominant oncogenic potential of p53-172h in an in vivo setting by crossing the p53-172h transgene together with ...200111417997
glucocorticoid receptor-mediated chromatin remodeling in vivo.the compaction of dna into chromatin provides an additional level of gene regulation in eukaryotes that may not be available to prokaryotes. when packaged as chromatin, most promoters are transcriptionally repressed, and transcription factors have reduced access to their binding sites. the glucocorticoid receptor (gr) is a ligand-activated transcription factor that regulates the activity of genes involved in many physiological processes. to regulate eukaryotic genes, the gr binds to target sites ...200111420719
characterization of mouse mammary tumour virus-induced migration of lymphoid cells into lymph nodes.we previously found that mtv-2+ lymph nodes (ln) implanted into mtv-2- mice underwent marked hyperplasia owing to the influx of lymphocytes. ln grafts infected with exogenous mouse mammary tumour viruses (mmtv), mmtv(fm) transmitted by fm mice and mmtv-2 produced by mtv-2, also swelled in mmtv-free recipients. mtv-3 and mtv-7 also displayed this capability. mtv-2-induced ln hyperplasia was earlier in onset and greater in extent when major histocompatibility complex (mhc) class ii i-e was express ...200111422903
weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: an exploratory study in tumor-bearing mice.at least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. we hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss.200111423703
protein kinase ck2 in mammary gland tumorigenesis.protein kinase ck2 is a ubiquitous and evolutionarily conserved serine/threonine kinase that is upregulated in many human cancers and can serve as an oncogene in lymphocytes. recently, we have demonstrated that ck2 potentiates wnt/beta-catenin signaling in mammary epithelial cells. to determine whether ck2 overexpression contributes to mammary tumorigenesis, we have performed comparative studies of human and rat breast cancer specimens and we have engineered transgenic mice with dysregulated exp ...200111423974
specific protection against breast cancers by cyclin d1 ablation.breast cancer is the most common malignancy among women. most of these cancers overexpress cyclin d1, a component of the core cell-cycle machinery. we previously generated mice lacking cyclin d1 using gene targeting. here we report that these cyclin d1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes. however, animals lacking cyclin d1 remain fully sensitive to other oncogenic pathways of the mammary epithelium, such as those driven by c-myc or wnt-1. our analy ...200111429595
interleukin-2 inhibits glucocorticoid receptor transcriptional activity through a mechanism involving stat5 (signal transducer and activator of transcription 5) but not ap-1.cytokines and glucocorticoids (gcs) signaling pathways interfere with each other in the regulation of apoptosis and gene expression in the immune system. interleukin-2 (il-2), through the janus kinase/signal transducers and activators of transcription (jak/stat) and mitogen-activated protein kinase (mapk) pathways, activates stat5 and activated protein-1 (ap-1) transcription factors, respectively, which are known to repress glucocorticoid receptor (gr) activity, at least in part, through protein ...200111435608
steroid hormone receptor-mediated histone deacetylation and transcription at the mouse mammary tumor virus promoter.acetylation of lysines in histones h3 and h4 n-terminal tails is associated with transcriptional activation and deacetylation with repression. our studies with the mouse mammary tumor virus (mmtv) promoter in chromatin show significant levels of acetylation at promoter proximal and distal regions prior to transactivation. upon activation with glucocorticoids or progestins, promoter proximal histones become deacetylated within the region of inducible nuclease hypersensitivity. the deacetylation l ...200111448945
large-scale chromatin decondensation and recondensation regulated by transcription from a natural promoter.we have examined the relationship between transcription and chromatin structure using a tandem array of the mouse mammary tumor virus (mmtv) promoter driving a ras reporter. the array was visualized as a distinctive fluorescent structure in live cells stably transformed with a green fluorescent protein (gfp)-tagged glucocorticoid receptor (gr), which localizes to the repeated mmtv elements after steroid hormone treatment. also found at the array by immunofluorescence were two different steroid r ...200111448988
[an antigen related to the mouse mammary cancer virus env gene product, detected in human lymphocytes, is associated with human breast cancer].expression of dna sequences homologous to sequences of env gene of mouse mammary tumor virus (mmtv) in the lymphocytes of patients with breast cancer and in subjects at a high risk of breast cancer has been reported. antigen analogous to envelope protein gp52, product of mmtv env gene, is detected in t lymphocytes of virtually all patients with breast cancer and extremely rarely in t cells of controls, where its expression is confined to b cells. for explaining such unexpected results, we studie ...200111449801
identification and characterization of metal ion binding sites in rna. 200111460561
identification of key amino acids of the mouse mammary tumor virus superantigen involved in the specific interaction with t-cell receptor v(beta) domains.mouse mammary tumor virus (mmtv) is a retrovirus encoding a superantigen that is recognized in association with major histocompatibility complex class ii by the variable region of the beta chain (v(beta)) of the t-cell receptor. the c-terminal 30 to 40 amino acids of the superantigen of different mmtvs display high sequence variability that correlates with the recognition of particular t-cell receptor v(beta) chains. interestingly, mmtv(sim) and mtv-8 superantigens are highly homologous but have ...200111462017
histone h1 phosphorylation by cdk2 selectively modulates mouse mammary tumor virus transcription through chromatin remodeling.transcriptional activation of the mouse mammary tumor virus (mmtv) promoter by ligand-bound glucocorticoid receptor (gr) is transient. previously, we demonstrated that prolonged hormone exposure results in displacement of the transcription factor nuclear factor 1 (nf1) and the basal transcription complex from the promoter, the dephosphorylation of histone h1, and the establishment of a repressive chromatin structure. we have explored the mechanistic link between histone h1 dephosphorylation and ...200111463824
notch signaling in mammary gland tumorigenesis.the notch receptor protein and its signaling pathway have been well conserved throughout evolution and appear to be pivotal components in cell fate decisions during development. recent studies suggest that, depending on the cellular and developmental context, notch signaling may also affect cell proliferation and programmed cell death. mammals have four related notch genes. one of these, designated notch-4, was found to be a common integration site for the mouse mammary tumor virus in mouse mamm ...200111467450
hormone-mediated dephosphorylation of specific histone h1 isoforms.we have previously shown a connection between histone h1 phosphorylation and the transcriptional competence of the hormone inducible mouse mammary tumor virus (mmtv) promoter. prolonged exposure of mouse cells to dexamethasone concurrently dephosphorylated histone h1 and rendered the mmtv promoter refractory to hormonal stimulation and, therefore, transcriptionally unresponsive. using electrospray mass spectrometry, we demonstrate here that prolonged dexamethasone treatment differentially effect ...200111479299
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
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
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
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