| l-carnitine: a nutritional modulator of glucocorticoid receptor functions. | l-carnitine is an essential nutrient with a major role in cellular energy production. there is evidence that, at high doses, l-carnitine might mimic some of the biological activities of glucocorticoids, especially immunomodulation. to explore the molecular basis of this effect, we tested the influence of l-carnitine on glucocorticoid receptor-alpha (gralpha) functions. millimolar concentrations of l-carnitine, which were not cytotoxic in vitro, significantly reduced the whole cell binding of [3h ... | 2003 | 12824292 |
| does a betaretrovirus infection trigger primary biliary cirrhosis? | patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. previous serologic studies have provided evidence to suggest a viral association with primary ... | 2003 | 12832623 |
| chromatin-dependent regulation of the mmtv promoter by camp signaling is mediated through distinct pathways. | the nucleoprotein structure of the mouse mammary tumor virus (mmtv) promoter defines its response to camp signaling. a stably replicating mmtv template in highly organized chromatin is repressed in the presence of camp, whereas a transiently transfected template with a disorganized structure is activated. in this study, we investigate the nature of the camp-induced signal(s) by which these opposing responses occur to gain insight into their mechanism. we demonstrate that the transcriptional chan ... | 2003 | 12837291 |
| formation of higher-order secondary and tertiary chromatin structures by genomic mouse mammary tumor virus promoters. | agarose multigel electrophoresis has been used to characterize the structural features of isolated genomic mouse mammary tumor virus (mmtv) promoters. the mouse 3134 cells used for these studies contain approximately 200 stably integrated tandem repeats of a 2.4-kb mmtv promoter fragment. inactive, basally active, and hormonally activated genomic promoters were liberated by restriction digestion of isolated nuclei, recovered in low-salt nuclear extracts, and electrophoresed in multigels consisti ... | 2003 | 12842912 |
| zonal expression of dickkopf-3 and components of the wnt signalling pathways in the human adrenal cortex. | the mechanisms underlying the differentiation of the adrenal cortex into zones are unclear. microarray studies on rna from microdissected zona reticularis (zr) and zona fasciculata/zona glomerulosa (zf/zg) derived from adult human adrenal glands showed that a gene of the dickkopf family (dkk), dkk3, is differentially expressed in the zones. the dickkopf proteins are morphogens involved in wnt signalling. northern blotting showed higher dkk3 transcript levels in zf/zg than zr samples. in situ hyb ... | 2003 | 12844346 |
| metastasis of transgenic breast cancer in plasminogen activator inhibitor-1 gene-deficient mice. | the plasminogen activator inhibitor-1 (pai-1) blocks the activation of plasmin(ogen), an extracellular protease vital to cancer invasion. pai-1 is like the corresponding plasminogen activator upa (urokinase-type plasminogen activator) consistently expressed in human breast cancer. paradoxically, high levels of pai-1 as well as upa are equally associated with poor prognosis in cancer patients. pai-1 is thought to play a vital role for the controlled extracellular proteolysis during tumor neovascu ... | 2003 | 12853975 |
| alternative mammary oncogenic pathways are induced by d-type cyclins; mmtv-cyclin d3 transgenic mice develop squamous cell carcinoma. | the three human d-type cyclins, cyclin d1, d2 and d3 share the ability to bind to and activate cdk4 and 6. mmtv-cyclin d1 transgenic mice develop mainly adenocarcinoma, while mmtv-cyclin d2 mice show a lack of alveologenesis during pregnancy and only develop carcinoma at low frequency. the effect of cyclin d3 overexpression in mammary glands remains hitherto unknown. we generated mmtv-cyclin d3 transgenic mice and report here that they develop exclusively squamous cell carcinoma. we show that al ... | 2003 | 12853979 |
| paradoxical triiodothyronine suppression of s14 transcription in permanent hepatic cell lines. | both in vivo and in primary rat hepatocyte culture, carbohydrate and triiodothyronine (t(3)) rapidly induce transcription of the rat s14 gene. to determine if regulation of this gene by t(3) is similar in human liver cells, we transfected the s14 upstream region into hepg2 cells. we chose this cell line because many others have used this cell line to study the effect of thyroid hormone on hepatic gene expression. we found that changing media glucose concentration did not affect s14 transcription ... | 2003 | 12855010 |
| mouse mammary tumor virus and the immune system. | mouse mammary tumor virus (mmtv) is a nonacute transforming retrovirus that causes mammary tumors in susceptible strains of mice. upon milk-borne transmission, b cells in the gut become infected and subsequently present a virus-encoded superantigen to cognate t cells. these t cells become activated and, in turn, stimulate neighboring lymphocytes, thereby establishing an infection-competent reservoir of lymphoid cells. during puberty and pregnancy, mammary epithelial cells actively divide, and vi ... | 2003 | 12857990 |
| her-2 dna and protein vaccines containing potent th cell epitopes induce distinct protective and therapeutic antitumor responses in her-2 transgenic mice. | overexpression of the growth factor receptor her-2 (c-erbb-2, neu) has transforming potential and occurs in approximately 20-30% of breast and ovarian cancers. her-2 is a self ag, but abs and t cells specific for her-2 have been isolated from cancer patients, suggesting her-2 may be a good target for active immunotherapy. we constructed rat her-2 dna and protein vaccines containing potent th cell epitopes derived from tetanus toxin and studied their potency in two strains of mice transgenic for ... | 2003 | 12874253 |
| inhibition of mmtv transcription by hdac inhibitors occurs independent of changes in chromatin remodeling and increased histone acetylation. | increased histone acetylation has been associated with activated gene transcription and decreased acetylation with repression. however, there is a growing number of genes known, which are downregulated by histone deacetylase (hdac) inhibitors through unknown mechanisms. this study examines the mechanism by which the mouse mammary tumor virus (mmtv) promoter is repressed by the hdac inhibitor, trichostatin a (tsa). we find that this repression is transcriptional in nature and that it occurs in th ... | 2003 | 12894222 |
| mouse mammary tumor virus c-rel transgenic mice develop mammary tumors. | amplification, overexpression, or rearrangement of the c-rel gene, encoding the c-rel nf-kappab subunit, has been reported in solid and hematopoietic malignancies. for example, many primary human breast cancer tissue samples express high levels of nuclear c-rel. while the rev-t oncogene v-rel causes tumors in birds, the ability of c-rel to transform in vivo has not been demonstrated. to directly test the role of c-rel in breast tumorigenesis, mice were generated in which overexpression of mouse ... | 2003 | 12897145 |
| estrogen receptor-dependent proteasomal degradation of the glucocorticoid receptor is coupled to an increase in mdm2 protein expression. | glucocorticoids and estrogens regulate a number of vital physiological processes. we developed a model breast cancer cell line, mcf-7 m, to examine potential mechanisms by which the ligand-bound estrogen receptor (er) regulates glucocorticoid receptor (gr)-mediated transcription. mcf-7 cells, which endogenously express eralpha, were stably transfected with mouse mammary tumor virus promoter-luciferase (mmtv-luc) reporter and gr expression constructs. our results demonstrate that treatment with e ... | 2003 | 12897156 |
| mammary carcinoma suppression by cellular retinoic acid binding protein-ii. | retinoic acid (ra) modulates cell proliferation, differentiation, and apoptosis, and is used in chemotherapy and chemoprevention in several human cancers. ra exerts its pleiotropic activities by activating the nuclear receptors, retinoic acid receptor (rar), which, in turn, regulate transcription of multiple target genes. in cells, ra also associates with cellular ra-binding proteins [cellular ra binding proteins (crabps)-i and -ii]. recent studies revealed that crabp-ii functions by "channeling ... | 2003 | 12907615 |
| passive immunization with neutralizing antibodies interrupts the mouse mammary tumor virus life cycle. | mouse mammary tumor virus (mmtv) infects the host via mucosal surfaces and exploits the host immune system for systemic spread and chronic infection. we have tested a neutralizing rat monoclonal antibody specific for the retroviral envelope glycoprotein gp52 for its efficiency in preventing acute and chronic mucosal and systemic infection. the antibody completely inhibits the superantigen response and chronic viral infection following systemic or nasal infection. surprisingly however, the antibo ... | 2003 | 12915552 |
| inappropriate p-cadherin expression in the mouse mammary epithelium is compatible with normal mammary gland function. | cadherins comprise a family of cell-cell adhesion proteins critical to the architecture and function of tissues. expression of family members e-, n-, and p-cadherin is regulated in a spatial and temporal fashion in the developing and adult organism. using in vivo and in vitro experimental systems, perturbation of cadherin expression by genetic deletion, overexpression, mutant dominant-negative constructs, and, to a lesser degree, expression of an inappropriate cadherin have all been shown to alt ... | 2003 | 12919105 |
| bacterial superantigens. | | 2003 | 12930353 |
| specificity of cyclin d1 for androgen receptor regulation. | androgen receptor (ar) activity is required for prostate growth, differentiation, and secretion. deregulation of ar activity results in inappropriate mitogenic signaling and is thought to contribute both to the initiation and progression of prostate cancers. cyclin d1 functions as a strong ar corepressor by directly interacting with and inhibiting receptor activity. however, the extent to which cyclin d1 functions to inhibit ar activity under conditions associated with cancer progression has not ... | 2003 | 12941814 |
| gene expression profiling of neu-induced mammary tumors from transgenic mice reveals genetic and morphological similarities to erbb2-expressing human breast cancers. | numerous studies have shown that the overexpression and amplification of erbb2/neu are observed in 20-30% of patients afflicted with breast cancer. furthermore, it has also been observed that the elevated expression of erbb2/neu also correlates with poor prognosis and clinical outcome. given the prevalence of this disease, we sought to create mouse models that mimic the human condition. in this study, we compared two mouse models expressing activated neu under the control of the endogenous and m ... | 2003 | 12941816 |
| the leader peptide of mmtv env precursor localizes to the nucleoli in mmtv-derived t cell lymphomas and interacts with nucleolar protein b23. | we have previously described two nucleolar proteins, named p14 and p21, in mmtv-induced t cell lymphomas. these proteins were identified by a monoclonal antibody (m-66) generated from a nontumorigenic, immunogenic variant of s49 t cell lymphoma. while p14 was common to several mmtv-derived t cell lymphomas, p21 was found only in highly tumorigenic variants of s49 cells. here we report that p14 is the leader peptide of the mmtv env precursor. the epitope recognized by m-66 contains a putative nuc ... | 2003 | 12951018 |
| identification of the receptor binding domain of the mouse mammary tumor virus envelope protein. | mouse mammary tumor virus (mmtv) is a betaretrovirus that infects rodent cells and uses mouse transferrin receptor 1 for cell entry. to characterize the interaction of mmtv with its receptor, we aligned the mmtv envelope surface (su) protein with that of friend murine leukemia virus (f-mlv) and identified a putative receptor-binding domain (rbd) that included a receptor binding sequence (rbs) of five amino acids and a heparin-binding domain (hbd). mutation of the hbd reduced virus infectivity, a ... | 2003 | 12970432 |
| induction of mammary gland differentiation in transgenic mice by the fatty acid-binding protein mrg. | a mammary-derived growth inhibitor-related gene (mrg) was previously identified and characterized. mrg induces differentiation of mammary epithelial cells in vitro and its expression is associated with mammary differentiation. to further define the role of mrg on mammary gland differentiation, a mrg transgenic mice model under the control of mouse mammary tumor virus promoter was established and the effect of mrg on mammary gland differentiation was investigated at histological and molecular lev ... | 2003 | 12975368 |
| a new strain of the mouse mammary tumor virus. | | 1958 | 13529014 |
| the mutagenic potential of a single dna double-strand break in a mammalian chromosome is not influenced by transcription. | in eukaryotes, dna double-strand breaks (dsbs) are repaired by competing hr and non-homologous end-joining (nhej) pathways. dsb repair by hr is highly accurate, while nhej can result in deletions and insertions. transcription enhances certain dna repair pathways and spontaneous homologous recombination (hr). as a means to promote accurate repair in active genes, we thought it possible that the balance between hr and nhej would be shifted toward hr in highly transcribed regions. we tested this id ... | 2003 | 13679152 |
| a mutation in the mouse mammary tumor virus. | | 1960 | 13801251 |
| the mouse mammary tumor virus. | | 1962 | 13885510 |
| neutralization of the mouse mammary tumor virus by rabbit antisera against c3hf tissue. | | 1963 | 13971455 |
| new method for detection of mouse mammary tumor virus. i. influence of foster nursing on incidence of hyperplastic mammary nodules in balb/ccrgl mice. | | 1963 | 14043039 |
| new method for detection of mouse mammary tumor virus. ii. effect of administration of lactating mammary tissue extracts on incidence of hyperplastic mammary nodules in balb/ccrgl mice. | | 1963 | 14043040 |
| electrophoretic separation of the mouse mammary tumor virus. | | 1963 | 14071831 |
| transgenic mice expressing a dominant-negative mutant type ii transforming growth factor-beta receptor exhibit impaired mammary development and enhanced mammary tumor formation. | we have previously shown that expression of a dominant-negative type ii transforming growth factor-beta receptor (dniir) in mammary epithelium under control of the mmtv promoter/enhancer causes alveolar hyperplasia and differentiation in virgin mice. here we show that mmtv-dniir female mice have accelerated mammary gland differentiation during early pregnancy with impaired development during late pregnancy and lactation followed by delayed postlactational involution. mammary tumors, mostly carci ... | 2003 | 14507660 |
| high prevalence of mmtv-like env gene sequences in gestational breast cancer. | gestational breast cancer (bc) is generally associated with rapid growth and increased mortality. because the presence of mmtv-like sequences in bc has been associated with laminin receptor expression, a marker of poor prognosis, gestational bcs were analyzed for mmtv env gene-like sequences to explore whether mmtv-like sequences were also associated with its adverse outcome. whereas 30-38% of sporadic bc have the sequences, in gestational bc the prevalence is 62%. we suggest that hormonal respo ... | 2003 | 14514972 |
| mouse mammary tumor viruses expressed by riii/sa mice with a high incidence of mammary tumors interact with the v beta-2- and v beta-8-specific t cells during viral infection. | the mouse mammary tumor viruses (mmtvs) that induce mammary adenocarcinomas in mice are transmitted from mother to offspring through milk. mmtv infection results in the deletion of specific t cells as a consequence of interaction between the mmtv-encoded superantigen (sag) and specific v beta chains of the t cell receptor. the specificity and kinetics of t cell deletion for a number of highly oncogenic mmtvs, such as c3h- and gr-mmtvs, have been studied in great detail. some work has also been d ... | 2003 | 14517082 |
| steroid receptor rna activator stimulates proliferation as well as apoptosis in vivo. | steroid receptor rna activator (sra) is an rna that coactivates steroid hormone receptor-mediated transcription in vitro. its expression is strongly up-regulated in many human tumors of the breast, uterus, and ovary, suggesting a potential role in pathogenesis. to assess sra function in vivo, a transgenic-mouse model was generated to enable robust human sra expression by using the transcriptional activity of the mouse mammary tumor virus long terminal repeat. transgenic sra was expressed in the ... | 2003 | 14517287 |
| dual stromelysin-3 function during natural mouse mammary tumor virus-ras tumor progression. | in human carcinomas, stromelysin-3/matrix metalloproteinase 11 (st3, mmp11) expression by nonmalignant fibroblastic cells located in the immediate vicinity of cancer cells is a bad prognostic factor. using mouse models of primary tumors, it has been demonstrated that st3 is a key player during local invasion, favoring cancer cell survival in connective tissue through an antiapoptotic function. to investigate the st3 impact on additional phases of cancer cell invasion, we developed mammary gland ... | 2003 | 14522908 |
| angiogenesis impairment in id-deficient mice cooperates with an hsp90 inhibitor to completely suppress her2/neu-dependent breast tumors. | id proteins bind basic helix-loop-helix transcription factors and function as dominant negative inhibitors of gene expression. id1 and id3 are required for the recruitment of bone marrow-derived endothelial cell precursors and tumors transplanted into id-deficient mice demonstrate impaired angiogenesis. mouse mammary tumor virus-neu mice were bred with id1-/-id3+/- mice to ascertain the role of id1 and id3 in mammary tumorigenesis in a more physiologically relevant model. in mammary tumors from ... | 2003 | 14526102 |
| ecotropic murine leukemia viruses and exogenous mouse mammary tumor viruses are not essential for pristane-induced lupus. | | 2003 | 14558108 |
| dynamic properties of nucleosomes during thermal and atp-driven mobilization. | the fundamental subunit of chromatin, the nucleosome, is not a static entity but can move along dna via either thermal or enzyme-driven movements. here we have monitored the movements of nucleosomes following deposition at well-defined locations on mouse mammary tumor virus promoter dna. we found that the sites to which nucleosomes are deposited during chromatin assembly differ from those favored during thermal equilibration. taking advantage of this, we were able to track the movement of nucleo ... | 2003 | 14560021 |
| cell death in mmtv-c-myc transgenic mouse mammary tumors may not be typical apoptosis. | enforced expression of c-myc has been shown to serve as an apoptotic stimulus in cultured cells. prior studies have also demonstrated that several tissues expressing c-myc transgene display a large number of dead cells, although a morphologic or biochemical verification of apoptosis in these tissues has actually not been presented. in the present study, we examined the morphologic properties of cell death in the mammary tumors developed from mmtv-c-myc transgenic mice. we found that c-myc-expres ... | 2003 | 14563945 |
| transcription factor ap-2gamma stimulates proliferation and apoptosis and impairs differentiation in a transgenic model. | ap-2 transcription factors play pivotal roles in orchestrating embryonic development by influencing the differentiation, proliferation, and survival of cells. furthermore, ap-2 transcription factors have been implicated in carcinogenesis, a process where the normal growth and differentiation program of cells is disturbed. to experimentally address the potential involvement of ap-2 in mammary gland tumorigenesis, we generated mice overexpressing ap-2gamma by transgenesis using the mouse mammary t ... | 2003 | 14573793 |
| introduction of estrogen receptor-alpha into the tta/tag conditional mouse model precipitates the development of estrogen-responsive mammary adenocarcinoma. | conditional expression of estrogen receptor (er)-alpha) was introduced into tetracycline-responsive mmtv-tta/tetop-tag mice to develop a mouse model of estrogen-responsive er-alpha-positive mammary adenocarcinoma. mammary adenocarcinomas developed in the mice with a mean latency of 11 months. precursor lesions including ductal hyperplasia and hyperplastic alveolar nodules were present by the age of 4 months. the mammary adenocarcinomas exhibited histological features similar to human breast canc ... | 2003 | 14578170 |
| preclinical evaluation of the tyrosine kinase inhibitor su11248 as a single agent and in combination with "standard of care" therapeutic agents for the treatment of breast cancer. | su11248 is an oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities through targeting platelet-derived growth factor receptor, vascular endothelial growth factor receptor, kit, and flt3, the first three of which are expressed in human breast cancer and/or its supporting tissues. the purpose of the present studies was to demonstrate the potent anticancer activity of su11248 alone or in combination with conventional cytotoxic agents against several distinct prec ... | 2003 | 14578466 |
| positron emission tomography agent 2-deoxy-2-[18f]fluoro-d-glucose has a therapeutic potential in breast cancer. | novel approaches are needed for breast cancer patients in whom standard therapy is not effective. 2-deoxy-2-[18f]fluoro-d-glucose (18f-fdg) was evaluated as a potential radiomolecular therapy agent in breast cancer animal models and, retrospectively, in patients with metastatic breast cancer. | 2003 | 14580255 |
| expression of tgf-beta type ii receptor antisense rna impairs tgf-beta signaling in vitro and promotes mammary gland differentiation in vivo. | in order to clarify the role of tgf-beta in mammary development and tumorigenesis, we investigated the efficacy of full- or partial-length tbetarii antisense rna specifically to reduce tbetarii levels in both in vitro and in vivo model systems. here we show that the expression of tbetarii antisense rna in vitro reduced tbetarii cell surface expression and inhibited the antiproliferative and transcriptional responses to exogenous tgf-beta. expression of full-length tbetarii antisense rna in a tra ... | 2003 | 14601051 |
| targeted expression of activated rac3 in mammary epithelium leads to defective postlactational involution and benign mammary gland lesions. | rac3, a novel member of the rho subfamily of the small gtpases, is frequently activated in cultured breast cancer cells and has been shown to mediate its effect via the p21-activated kinase (pak) pathway. in order to evaluate these findings in vivo, we generated transgenic mice that express human constitutively active v12rac under the control of the mouse mammary tumor virus (mmtv) promoter, which targets the transgene expression to the mammary epithelium. v12rac3 expression could be detected du ... | 2003 | 14605486 |
| the eukaryotic translation initiation factor 4gi is cleaved by different retroviral proteases. | the initiation factor eif4g plays a central role in the regulation of translation. in picornaviruses, as well as in human immunodeficiency virus type 1 (hiv-1), cleavage of eif4g by the viral protease leads to inhibition of protein synthesis directed by capped cellular mrnas. in the present work, cleavage of both eif4gi and eif4gii has been analyzed by employing the proteases encoded within the genomes of several members of the family retroviridae, e.g., moloney murine leukemia virus (momlv), mo ... | 2003 | 14610163 |
| increased malignancy of neu-induced mammary tumors overexpressing active transforming growth factor beta1. | to determine if neu is dominant over transforming growth factor beta (tgf-beta), we crossed mouse mammary tumor virus (mmtv)-neu mice with mmtv-tgf-beta1(s223/225) mice expressing active tgf-beta1 in the mammary gland. bigenic (nt) and neu-induced mammary tumors developed with a similar latency. the bigenic tumors and their metastases were less proliferative than those occurring in mmtv-neu mice. however, nt tumors exhibited less apoptosis and were more locally invasive and of higher histologica ... | 2003 | 14612410 |
| examination of tumour histopathology and gene expression in a neu/s100a4 transgenic model of metastatic breast cancer. | elevated levels of the calcium-binding protein s100a4 have been causally linked to the metastatic spread of breast cancer cells in several in vitro and in vivo model systems and, more recently, correlated with patient death in a series of human breast cancer specimens. in transgenic mice expressing mmtv-neu transgenes in mammary gland, additional expression of s100a4 transgenes results in an enhanced metastatic capability. despite this phenotypic difference arising from elevated s100a4, it is no ... | 2003 | 14632631 |
| glucocorticoid inhibition of sp-a gene expression in lung type ii cells is mediated via the ttf-1-binding element. | induction of surfactant protein-a (sp-a) gene expression in fetal lung type ii cells by camp and il-1 is mediated by increased binding of thyroid transcription factor-1 (ttf-1) and nf-b proteins p50 and p65 to the ttf-1-binding element (tbe) at -183 bp. in type ii cell transfections, dexamethasone (dex) markedly inhibits camp-induced expression of rabbit sp-a:human growth hormone (hgh) fusion genes containing as little as 300 bp of the sp-a 5'-flanking sequence. dex inhibition is blocked by ru-4 ... | 2004 | 14633512 |
| complex effects of ras proto-oncogenes in tumorigenesis. | ras proteins have been found mutated in about one-third of human tumors. in vitro, ras has been shown to regulate distinct and contradictory effects, such as cellular proliferation and apoptosis. nonetheless, the effects that the wild-type protein elicits in tumorigenesis are poorly understood. depending on the type of tissue, ras proto-oncogenes appear to either promote or inhibit the tumor phenotype. in this report, we treated wild-type and n-ras knockout mice with 3-methylcholanthrene (mca) t ... | 2004 | 14633661 |
| stem cell recruitment and liver de-differentiation in mmtv-neu (erbb-2) transgenic mice. | the liver of tumor-bearing hosts manifests fetal phenotypes. we investigated the expression of differentiation markers on the liver in mmtv-neu (erbb-2) transgenic mice, in the period from incipient neoangiogenesis to lung metastatization. we report afp expression by hepatocytes in all lobular zones, cd34 cell arrest and subsequent hemopoiesis in periportal and mid-zone areas, oval-like cells (cd34+, ck19+, afp+) and ductular reaction in portal tracts, portal ck19+ and ggt+ hepatoblast-like cell ... | 2003 | 14666678 |
| evidence that transgenes encoding components of the wnt signaling pathway preferentially induce mammary cancers from progenitor cells. | breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. here we report that mammary tumors induced by components of the wnt signaling pathway contain heterogeneous cell types and express early developmental markers, in contrast to tumors induced by other signaling elements. expression of the wnt-1 protooncogene in mammary glands of transgenic mice expands ... | 2003 | 14668450 |
| epidermal growth factor receptor-dependent activation of gab1 is involved in erbb-2-mediated mammary tumor progression. | activation of the epidermal growth factor receptor (egfr) family is thought to play an important role in mammary tumorigenesis and metastasis. the potent transforming activity of the egfr family is due to their ability to heterodimerize with each other in response to a number of mitogenic ligands. the formation of egfr and erbb-2 heterodimers has been recently implicated as an important factor in the induction of sporadic human breast cancers. to directly assess whether the catalytic activity of ... | 2003 | 14668796 |
| transplanted bone marrow cells preferentially home to the vessels of in situ generated murine tumors rather than of normal organs. | transplanted bone marrow-derived (bm) cells have been shown to home into the tumor vessels of s.c. implanted tumor models and to functionally contribute to tumor neoangiogenesis and tumor growth. however, whether bm cells contribute to the vessels of in situ developing tumors remains unknown. we have taken advantage of the in situ generation of mammary tumors in transgenic mice carrying the polyoma virus middle t oncogene (mmtv-pyvt) to determine whether transplanted bm cells home to and incorpo ... | 2004 | 14688394 |
| toll-like receptor 4-dependent activation of dendritic cells by a retrovirus. | mouse mammary tumor virus (mmtv) is a milk-borne retrovirus that exploits the adaptive immune system. it has recently been shown that mmtv activates b cells via toll-like receptor 4 (tlr4), a molecule involved in innate immune responses. here, we show that direct virus binding to tlr4 induced maturation of bone marrow-derived dendritic cells and up-regulated expression of the mmtv entry receptor (cd71) on these cells. in vivo, mmtv increased the number of dendritic cells in neonatal peyer's patc ... | 2004 | 14694089 |
| riii/sa mice with a high incidence of mammary tumors express two exogenous strains and one potential endogenous strain of mouse mammary tumor virus. | the inbred mouse strain riii has long been known for shedding large amounts of mouse mammary tumor virus (mmtv) particles in milk and for the development of hormone-dependent early mammary tumors at a very high incidence (>90%). we have established one riii subline (riii/sa) that shows a pattern of virus expression and tumor incidence similar to that in riii mice. in the present study, we analyzed the milk and mammary tumors of riii/sa mice for virus characterization by reverse transcriptase pcr ... | 2004 | 14694140 |
| geranylgeranyltransferase i inhibitor ggti-2154 induces breast carcinoma apoptosis and tumor regression in h-ras transgenic mice. | treatment of h-ras transgenic mice with the geranylgeranyltransferase i (ggtase i) inhibitor ggti-2154 results not only in halting the growth of aggressive breast tumors but actually in inducing the regression (54 +/- 3%) of all 19 tumors analyzed. the farnesyltransferase (ftase) inhibitor fti-2148 induced an average of 87 +/- 3% regression in the 13 tumors analyzed. ggtase i, but not ftase, is inhibited in breast tumors after treatment with ggti-2154, whereas in tumors from mice treated with ft ... | 2003 | 14695209 |
| early parity significantly elevates mammary tumor incidence in mmtv-c-myc transgenic mice. | female transgenic mice, in which a murine c-myc gene has been placed under the transcriptional control of the mouse mammary tumor virus long terminal repeat, are prone to developing mammary adenocarcinomas. owing to the manner in which these mammary tumors develop, it is clear that exogenous expression of the c-myc transgene is necessary to but insufficient for murine mammary tumorigenesis. the genetic background of study mice has been shown to influence the phenotype induced by different transg ... | 2003 | 14713205 |
| angiogenic acceleration of neu induced mammary tumor progression and metastasis. | the neu (erbb2, her2) member of the epidermal growth factor receptor family is implicated in many human breast cancers. we have tested the importance of increased angiogenic signaling in the neuyd [mouse mammary tumor virus (mmtv)-neu(ndl)-yd5] mammary tumor model. transgenic mice expressing vascular endothelial growth factor (vegf)(164) from the mmtv promoter were generated. these mice expressed vegf(164) rna and protein at 20- to 40-fold higher levels throughout mammary gland development but e ... | 2004 | 14729621 |
| opposite effects of clozapine and sulpiride on the lipopolysaccharide-induced inhibition of the gr-mediated gene transcription in fibroblast cells. | previously, we have found that some antipsychotic drugs are able to inhibit glucocorticoid receptor (gr)-mediated gene transcription. since these drugs are known not only to inhibit hypothalamic-pituitary-adrenal (hpa) axis activity, but also to modulate the immunological system, the aim of the present study was to compare the effect of sulpiride and clozapine on gr function under basal culture conditions and during activation by lipopolysaccharide (lps). the effect of clozapine and sulpiride al ... | 2003 | 14730115 |
| leptin receptor-deficient mmtv-tgf-alpha/lepr(db)lepr(db) female mice do not develop oncogene-induced mammary tumors. | being overweight is a risk factor for postmenopausal breast cancer and is associated with an increased incidence and shortened latency of spontaneous and chemically induced mammary tumors in rodents. however, leptin-deficient obese lep(ob)lep(ob) female mice have reduced incidences of spontaneous and oncogene-induced mammary tumors. of interest, leptin enhances the proliferation of human breast cancer cell lines in which leptin receptors are expressed, which suggests that leptin signaling plays ... | 2004 | 14734797 |
| downregulation of muc1 in mmtv-c-neu tumors. | muc1 is a tumor antigen, overexpressed in approximately 90% of human breast cancers. in normal glandular epithelia, muc1 is expressed at the apical surface; however, in carcinomas an aberrantly glycosylated form of muc1 is upregulated and expressed around the entire surface of the cell. previously, we have shown that a lack of muc1 significantly delays tumor progression and/or onset in mmtv-pyv-mt and mmtv-wnt-1 transgenic mice. here we show that, unlike the models mentioned above, a loss of muc ... | 2004 | 14737104 |
| progesterone receptor deficient in chromatin binding has an altered cellular state. | our previous work has shown that the progesterone receptor (pr) can exist in two distinct functional states in mammary adenocarcinoma cells. the differences in function included the ability to activate a promoter in organized chromatin, sensitivity to ligand, and ligand-independent activation. to determine whether these functional differences were because of altered cellular processing, we carried out biochemical analyses of the functionally distinct prs. although the majority of pr is localized ... | 2004 | 14744870 |
| retrovirus infection as a trigger for primary biliary cirrhosis? | | 2004 | 14751695 |
| cloning the human betaretrovirus proviral genome from patients with primary biliary cirrhosis. | patients with primary biliary cirrhosis (pbc) have both serologic and tissue evidence of infection. a recently identified human betaretrovirus was originally cloned from the biliary epithelium cdna library of a patient with pbc. by conducting a blastn search, the initial partial pol gene fragment was found to have 95% to 97% nucleotide homology with mouse mammary tumor virus (mmtv) and with retrovirus sequences derived from human breast cancer samples. using an anti-p27(ca) mmtv antibody, viral ... | 2004 | 14752833 |
| correspondence re: c. ford, et al. mouse mammary tumor virus-like gene sequences in breast tumors of australian and vietnamese women. clin. cancer res., 9: 1118-1120, 2003. | | 2004 | 14760104 |
| antibodies reactive with the mouse mammary tumor virus in sera of breast cancer patients. | igg binding to purified mouse mammary tumor virus (mumtv) was quantitated by an enzyme-linked immunoassay (elisa) using sera from patients with breast cancer or benign breast disease, or from healthy age-matched controls. significantly greater binding (p<0.01) was found in breast-cancer-derived sera than in the other categories. in addition to igg reactivity, three breast cancer sera also possessed iga and igm reactive with mumtv by the elisa assay. only igg was reactive in the majority of sera ... | 1980 | 14768700 |
| transforming growth factor beta enhances the glucocorticoid response of the mouse mammary tumor virus promoter through smad and ga-binding proteins. | tissue-specific transcription is advantageously investigated by using viral promoters, which are selected for compact regulatory elements. mouse mammary tumor virus (mmtv) has adapted to specialized cell types and targets initially b lymphocytes. we previously showed that, in b-cell lines, glucocorticoid-induced mmtv transcription requires an ets family factor, ga-binding protein (gabp), bound in tandem to the mmtv dna next to the glucocorticoid receptor (gr). we now report that transforming gro ... | 2004 | 14963116 |
| cryoelectron microscopy of mouse mammary tumor virus. | cryoelectron microscopy of mouse mammary tumor virus, a betaretrovirus, provided information about glycoprotein structure and core formation. the virions showed the broad range of diameters typical of retroviruses. betaretroviruses assemble cytoplasmically, so the broad size range cannot reflect the use of the plasma membrane as a platform for assembly. | 2004 | 14963166 |
| accidental passengers or perpetrators? current virus-cancer research. | | 2004 | 14970272 |
| human murine mammary tumour virus-like agents are genetically distinct from endogenous retroviruses and are not detectable in breast cancer cell lines or biopsies. | it has been reported that a human murine mammary tumour virus (mmtv)-like virus (hmlv), which may be an endogenous human retrovirus (herv), occurs in the human breast cancer cell lines t47d and mcf-7 and, in 38% of human breast cancer biopsies. as the aetiology of most breast cancers remains unknown, it is important to verify these observations in differing breast cancer populations worldwide. thus, we sought to determine the genetic relationships between hmlvs, mmtvs, and hervs, and to investig ... | 2004 | 14972564 |
| genetically engineered mouse models of mammary intraepithelial neoplasia. | foci of atypical mammary epithelium have been associated with breast cancer in many species including mouse and man. the advent of targeted genomics has led to the creation of numerous genetically engineered mice (gem) which display focal atypical lesions associated with mammary cancer. some early lesions in gem have a remarkable morphological similarity to pre-cancers in humans. while the malignant potential of atypical foci have been thoroughly documented in the non-gem by tissue transplantati ... | 2000 | 14973386 |
| biophysical analysis of specific genomic loci assembled as chromatin in vivo. | | 2004 | 14975296 |
| the role of the cyclin d1-dependent kinases in erbb2-mediated breast cancer. | intact cyclin d1 functions are essential for transformation by erbb2 in tissue culture and murine models. because cyclin d1 may alter cell proliferation through a variety of mechanisms, we used transgenic models and human tumor samples to particularly address the role of cyclin d1-cyclin-dependent kinases in transformation by erbb2. the p16 tumor suppressor specifically blocks cyclin-dependent kinase 4 and 6 activity. here we show that an mmtv-p16 transgene blocked tumorigenesis by erbb2, demons ... | 2004 | 14982856 |
| differential recruitment of nuclear receptor coactivators may determine alternative rna splice site choice in target genes. | the biological consequences of steroid hormone-mediated transcriptional activation of target genes might be difficult to predict because alternative splicing of a single neosynthesized precursor rna can result in production of different protein isoforms with opposite biological activities. therefore, an important question to address is the manner in which steroid hormones affect the splicing of their target gene transcripts. in this report, we demonstrate that individual steroid hormones had dif ... | 2004 | 14982999 |
| inactivation of the wip1 phosphatase inhibits mammary tumorigenesis through p38 mapk-mediated activation of the p16(ink4a)-p19(arf) pathway. | modulation of tumor suppressor activities may provide new opportunities for cancer therapy. here we show that disruption of the gene ppm1d encoding wip1 phosphatase activated the p53 and p16 (also called ink4a)-p19 (also called arf) pathways through p38 mapk signaling and suppressed in vitro transformation of mouse embryo fibroblasts (mefs) by oncogenes. disruption of the gene cdkn2a (encoding p16 and p19), but not of trp53 (encoding p53), reconstituted cell transformation in ppm1d-null mefs. in ... | 2004 | 14991053 |
| aib1/src-3 deficiency affects insulin-like growth factor i signaling pathway and suppresses v-ha-ras-induced breast cancer initiation and progression in mice. | although the amplified in breast cancer 1 (aib1) coactivator is amplified and overexpressed in breast cancers, its role in mammary carcinogenesis remains unknown. we demonstrate that during mammary development and tumorigenesis, the elevation of aib1 level and its nuclear localization correlate with normal and transformed mammary epithelial proliferation, whereas its lower expression and cytoplasmic localization correlate with mammary epithelial quiescence and differentiation. in this study, the ... | 2004 | 14996752 |
| trichostatin a reduces hormone-induced transcription of the mmtv promoter and has pleiotropic effects on its chromatin structure. | the deacetylase inhibitor trichostatin a (tsa) has long been used to study the relationship between gene transcription and the acetylation status of chromatin. we have used xenopus laevis oocytes to study the effects of tsa on glucocorticoid receptor (gr)-dependent transcription and we have related these effects to changes in the chromatin structure of a reporter mouse mammary tumor virus (mmtv) promoter. we show that tsa induces a low level of constitutive transcription. this correlates with a ... | 2004 | 15009194 |
| glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in jurkat acute lymphoblastic leukemia cells. | glucocorticoids (gc) induce apoptosis in malignant lymphoblasts, but the mechanism of this process as well as that of the clinically important gc resistance is unknown. we investigated gc resistance in jurkat t-all cells in which ectopic gc receptor (gr) restores gc sensitivity, suggesting deficient gr expression. jurkat cells expressed one wild-type and one mutated (r477h) gr allele. gr(r477h) ligand-binding-dependent nuclear import, as revealed by live-cell microscopy of yfp-tagged gr, was una ... | 2004 | 15017388 |
| rapid glucocorticoid receptor exchange at a promoter is coupled to transcription and regulated by chaperones and proteasomes. | exchange of the glucocorticoid receptor (gr) at promoter target sites provides the only known system in which transcription factor cycling at a promoter is fast, occurring on a time scale of seconds. the mechanism and function of this rapid exchange are unknown. we provide evidence that proteasome activity is required for rapid gr exchange at a promoter. we also show that chaperones, specifically hsp90, stabilize the binding of gr to the promoter, complicating models in which the associated chap ... | 2004 | 15024059 |
| chromatin-mediated restriction of nuclear factor 1/ctf binding in a repressed and hormone-activated promoter in vivo. | mouse mammary tumor virus (mmtv) promoter-driven transcription is induced by glucocorticoid hormone via binding of the glucocorticoid receptor (gr). the mmtv promoter also harbors a binding site for nuclear factor 1 (nf1). nf1 and gr were expressed in xenopus oocytes; this revealed gr-nf1 cooperativity both in terms of dna binding and chromatin remodeling but not transcription. a fraction of nf1 sites were occupied in a hormone-dependent fashion, but a significant and nf1 concentration-dependent ... | 2004 | 15024090 |
| brca2 deficiency does not impair mammary epithelium development but promotes mammary adenocarcinoma formation in p53(+/-) mutant mice. | brca2 is an important tumor suppressor associated with susceptibility to breast cancer. although increasing evidence indicates that the primary function of brca2 is to facilitate the repair of dna damage via the homologous recombination pathway, how brca2 prevents breast cancer is largely unknown. to study the role of brca2 specifically in mammary epithelium development, we crossed mice bearing the conditionally deficient allele brca2(flox9-10) to mouse mammary tumor virus- or whey acidic protei ... | 2004 | 15026330 |
| cell cycle-related variation in subcellular localization of eif3e/int6 in human fibroblasts. | the int-6 gene is a site of mouse mammary tumour virus (mmtv) integration in murine tumours and int6 protein has been identified independently as a subunit (eif3e) of the eukaryotic translation initiation factor eif3. in addition, the protein can interact with two other multi-subunit complexes: the cop9 signalosome (csn) and the proteasome. the role of int6 in tumourigenesis is nonetheless currently unclear. here, using immunofluorescence microscopy, we show that eif3e/int6 is localized in part ... | 2004 | 15030549 |
| understanding global changes in histone h1 phosphorylation using mass spectrometry. | histone post-translational modifications have been implicated in a variety of biological processes such as gene expression, dna replication, and chromatin assembly. the modifications include methylation, acetylation, phosphorylation, ubiquitination, glycosylation, and adp-ribosylation. for several years, we have been investigating the role of histone h1 phosphorylation in transcription using the hormone inducible mouse mammary tumor virus (mmtv) promoter. when mouse cells were exposed to prolong ... | 2004 | 15039087 |
| a viral aetiology for breast cancer: time to re-examine the postulate. | despite decades of research, no aetiologic factor(s) for human breast cancer has been identified and the search for a causal agent has all but been abandoned during the past thirty years. over 60 years ago, it was demonstrated that breast tumours in mice are caused by an oncornavirus, murine mammary tumour virus (mmtv). whilst many at that time postulated a similar virus might be the causative agent of human breast cancer, genetic evidence was difficult to obtain primarily because of the occurre ... | 2004 | 15044830 |
| reconstitution of glucocorticoid receptor-dependent transcription in vivo. | we developed a model system to study glucocorticoid receptor (gr)-mediated chromatin remodeling by the brg1 complex. introduction of the brg1 atpase into the sw-13 cell line initiates the formation of a functional remodeling complex. this complex is able to induce transcriptional activation from a transiently transfected promoter with wild-type and chromatin-remodeling-deficient brg1 mutants, suggesting that the complex possesses a coactivator function independent from remodeling. transactivatio ... | 2004 | 15060156 |
| characterization of a new class of selective nonsteroidal progesterone receptor agonists. | the identification of a new series of selective nonsteroidal progesterone receptor (pr) agonists is reported. using a high-throughput screening assay based on the measurement of transactivation of a mouse mammary tumor virus promoter-driven luciferase reporter (mmtv-luc) in human breast cancer t47d cells, a benzimidazole-2-thione analog was identified. compound 1 showed an apparent ec50 of 53 nm and efficacy of 93% with respect to progesterone. it binds to pr with high affinity (ki nm), but had ... | 2004 | 15072922 |
| her2-targeted therapy reduces incidence and progression of midlife mammary tumors in female murine mammary tumor virus huher2-transgenic mice. | this study examined the effectiveness of early and prolonged mu4d5 (the murine form of trastuzumab/herceptin) treatment in transgenic mice that overexpress human her2 (huher2), under the murine mammary tumor virus promoter, as a model of huher2-overexpressing breast cancer. | 2004 | 15073130 |
| rapid periodic binding and displacement of the glucocorticoid receptor during chromatin remodeling. | an ultrafast uv laser crosslinking assay has provided novel insights into the progression of the swi/snf-mediated chromatin-remodeling reaction and transcription factor binding in real time. we demonstrate site-specific crosslinking between the glucocorticoid receptor (gr), the hswi/snf chromatin-remodeling complex, and the mouse mammary tumor virus (mmtv) promoter assembled in an array of correctly positioned nucleosomes. gr first demonstrates rapid binding to the promoter and then is actively ... | 2004 | 15099516 |
| initial stages of mammary tumor virus infection are superantigen independent. | exogenous mouse mammary tumor virus (mmtv) is transmitted via the milk from infected mothers to newborn pups. efficient mmtv transmission is dependent on proliferation of t cells with particular tcr beta-chains, which occurs upon recognition of virally encoded superantigen (sag) bound to mhc class ii molecules. it is assumed that infection of these dividing cells favors mmtv amplification. sag is important for mmtv infection, as mice that lack sag-cognate t cells due to expression of endogenous ... | 2004 | 15100301 |
| a human murine mammary tumour virus-like agent is an unconvincing aetiological agent for human breast cancer. | there has recently been renewed interest in both the scientific literature, and in the media, that a human relative (hmlv) of murine mammary tumour virus (mmtv) may be implicated in the aetiology of up to 42% of sporadic cases of human breast cancer. such reports are potentially of considerable clinical significance, as aside from the small percentage of genetically acquired breast cancers, the cause of sporadic cases of breast cancer is completely unknown. indeed, convincing proof of an infecti ... | 2004 | 15124233 |
| activation of akt-1 (pkb-alpha) can accelerate erbb-2-mediated mammary tumorigenesis but suppresses tumor invasion. | elevated expression of akt-1 (pkbalpha) has been noted in a significant percentage of primary human breast cancers. another frequent event in the genesis of human breast cancers is amplification and overexpression of the erbb-2 receptor tyrosine kinase, an event which is associated with activation of akt-1. to directly assess the importance of akt-1 activation in erbb-2 mammary tumor progression, we interbred separate strains of transgenic mice carrying mouse mammary tumor virus/activated akt-1 ... | 2004 | 15126356 |
| the homeodomain protein cdp regulates mammary-specific gene transcription and tumorigenesis. | the ccaat-displacement protein (cdp) has been implicated in developmental and cell-type-specific regulation of many cellular and viral genes. we previously have shown that cdp represses mouse mammary tumor virus (mmtv) transcription in tissue culture cells. since cdp-binding activity for the mmtv long terminal repeat declines during mammary development, we tested whether binding mutations could alter viral expression. infection of mice with mmtv proviruses containing cdp binding site mutations e ... | 2004 | 15143175 |
| somatic mutation of p53 leads to estrogen receptor alpha-positive and -negative mouse mammary tumors with high frequency of metastasis. | approximately 70% of human breast cancers are estrogen receptor alpha (eralpha)-positive, but the origins of eralpha-positive and -negative tumors remain unclear. hormonal regulation of mammary gland development in mice is similar to that in humans; however, most mouse models produce only eralpha-negative tumors. in addition, these mouse tumors metastasize at a low rate relative to human breast tumors. we report here that somatic mutations of p53 in mouse mammary epithelial cells using the cre/l ... | 2004 | 15150107 |
| null mutation of peroxisome proliferator-activated receptor-interacting protein in mammary glands causes defective mammopoiesis. | to investigate the role of nuclear receptor coactivator peroxisome proliferator-activated receptor-interacting protein (prip) in mammary gland development, we generated a conditional null mutation of prip in mammary glands. in prip-deficient mammary glands, the elongation of ducts during puberty was not affected, but the numbers of ductal branches were decreased, a condition that persisted long after puberty, indicating that the potential of ductal branching was impaired. during pregnancy, prip- ... | 2004 | 15161927 |
| effects of nefazodone on the development of experimentally induced tumors in stressed rodents. | anxiety and depression are commonly encountered in patients with cancer and constitute risk and prognostic factors for the disease. although previous findings do not support an overall association between the use of antidepressants and higher prevalence of cancer, results for serotonin uptake inhibitors are not entirely reassuring. | 2004 | 15164159 |
| long-term exposure to elevated levels of circulating timp-1 but not mammary timp-1 suppresses growth of mammary carcinomas in transgenic mice. | tissue inhibitor of metalloproteinases-1 (timp-1) regulates matrix metalloproteinase activity, acts as a growth stimulator and inhibits apoptosis. we developed transgenic mice to evaluate the relevance of circulating versus mammary timp-1 in mammary carcinogenesis. the transgene was placed under the control of the albumin (alb) promoter for the production of large amounts of timp-1 in the liver and release into the systemic circulation to achieve chronically elevated blood levels. the initial 7, ... | 2004 | 15166086 |
| impaired alveologenesis and maintenance of secretory mammary epithelial cells in jak2 conditional knockout mice. | jak2 is a hormone-receptor-coupled kinase that mediates the tyrosine phosphorylation and activation of signal transducers and activators of transcription (stat). the biological relevance of jak2-stat signaling in hormone-responsive adult tissues is difficult to investigate since jak2 deficiency leads to embryonic lethality. we generated jak2 conditional knockout mice to study essential functions of jak2 during mammary gland development. the mouse mammary tumor virus-cre-mediated excision of the ... | 2004 | 15169911 |
| explant-cell culture of primary mammary tumors from mmtv-c-myc transgenic mice. | we have established an explant-cell culture system for mammary gland tumors from c-myc oncogene-expressing transgenic mice and potentially other transgenic strains. by coating culture dish surfaces with fetal bovine serum and using culture media supplemented with low serum and growth factors, the mammary tumor specimens could be maintained in culture for over 3 mo. throughout the culture period, the explants produced abundant outgrowths of epithelial cells. as the outgrowths of epithelial cells ... | 2004 | 15180438 |
| a mouse mammary tumor virus-like long terminal repeat superantigen in human breast cancer. | we previously reported a 660-bp mouse mammary tumor virus (mmtv)-like env gene sequence in approximately 38% of human breast cancer dna, but not in normal breasts or other tumors. this mmtv-like env gene sequence was expressed in 66% of the env gene-positive human breast cancers. an entire proviral structure was identified in human breast cancer dna with high homology to mmtv and low homology to known human endogenous retrovirus. mmtv-like long terminal repeat (ltr) sequences were also detected ... | 2004 | 15205319 |