| inactivation of fip200 leads to inflammatory skin disorder, but not tumorigenesis, in conditional knock-out mouse models. | fip200 (focal adhesion kinase family interacting protein of 200 kda) has been shown to interact with other proteins to regulate several intracellular signaling pathways. to study a potential role of fip200 in tumorigenesis and possibly other disease processes in vivo, we created and analyzed murine mammary tumor virus-cre-mediated fip200 conditional knock-out (cko) mice. we found that deletion of fip200 in mammary epithelial cells did not result in spontaneous development of breast cancer. moreo ... | 2009 | 19106106 |
| do viruses cause breast cancer? | because mouse mammary tumor virus (mmtv; the bittner virus) is the proven cause of breast cancer in both field and experimental mice, similar viruses have long been suspects as a potential cause of human breast cancer. mmtv-like viral genetic material has been identified in human breast tumors, but there is no definitive evidence whether mmtv is causal and not merely an innocuous infection in humans. high-risk human papilloma viruses (hpvs), epstein-barr (ebv), and other viruses also have been i ... | 2009 | 19109792 |
| combinatorial probabilistic chromatin interactions produce transcriptional heterogeneity. | gene regulation often appears deterministic in the average cell population, but transcription is a probabilistic process at the single-cell level. although many mechanisms are invoked to account for this behavior, it is difficult to determine how cell-to-cell variation in the interactions of transcription factors with target chromatin impact transcriptional output. here, we use cells that contain a 200-copy tandem array of promoter or reporter gene units to simultaneously visualize transient int ... | 2009 | 19126674 |
| targeting the activator protein 1 transcription factor for the prevention of estrogen receptor-negative mammary tumors. | the oncogene erbb2 is overexpressed in 20% to 30% human breast cancers and is most commonly overexpressed in estrogen receptor (er)-negative breast cancers. transgenic mice expressing erbb2 develop er-negative mammary tumors, mimicking human breast carcinogenesis. previously, we have shown that activator protein 1 (ap-1) regulates proliferation of er-negative breast cancer cells. we hypothesized that blockade of ap-1 in mouse mammary epithelial cells will suppress er-negative tumorigenesis induc ... | 2008 | 19138935 |
| combination chemoprevention of her2/neu-induced breast cancer using a cyclooxygenase-2 inhibitor and a retinoid x receptor-selective retinoid. | the inducible prostaglandin synthase isoform cyclooxygenase-2 (cox-2) is overexpressed in approximately 40% of human breast carcinomas and in precancerous breast lesions, particularly in association with overexpression of human epidermal growth factor receptor 2 (her2/neu). experimental breast cancer can be suppressed by pharmacologic inhibition or genetic ablation of cox-2, suggesting potential clinical utility of cox-2 inhibitors with respect to breast cancer. importantly, several clinical tri ... | 2008 | 19138958 |
| effect of lapatinib on the development of estrogen receptor-negative mammary tumors in mice. | lapatinib, a selective orally available inhibitor of epidermal growth factor receptor (egfr) and erbb2 receptor tyrosine kinases, is a promising agent for the treatment of breast cancer. we examined the effect of lapatinib on the development of mammary tumors in mmtv-erbb2 transgenic mice, which express wild-type erbb2 under the control of the mouse mammary tumor virus promoter and spontaneously develop estrogen receptor (er)-negative and erbb2-positive mammary tumors by 14 months of age. mice w ... | 2009 | 19141783 |
| inhibition of peroxisome proliferator-activated receptor gamma increases estrogen receptor-dependent tumor specification. | peroxisome proliferator-activated receptor gamma (ppargamma) is a nuclear receptor that regulates gene transcription associated with intermediary metabolism, adipocyte differentiation, and tumor suppression and proliferation. to understand the role of ppargamma in tumorigenesis, transgenic mice were generated with mammary gland-directed expression of the dominant-negative transgene pax8ppargamma. transgenic mice were phenotypically indistinguishable from wild-type (wt) mice, but mammary epitheli ... | 2009 | 19147585 |
| expression of murine apobec3 alleles in different mouse strains and their effect on mouse mammary tumor virus infection. | recent work has shown that mouse apobec3 restricts infection by mouse mammary tumor virus (mmtv) and murine leukemia virus (mlv) and that there are polymorphic apobec3 alleles found in different inbred mouse strains. for example, c57bl/6 mice, which are resistant to friend mlv (f-mlv), encode a apobec3 gene different from that encoded by f-mlv-susceptible balb/c mice; the predominant rna produced in c57bl/6 mice lacks exon 5 (ma3(-5)) and encodes a protein with 15 polymorphic amino acids. it has ... | 2009 | 19153233 |
| induction of apobec3 in vivo causes increased restriction of retrovirus infection. | apobec3 proteins are important cellular factors that restrict infection by a number of viruses, including human immunodeficiency virus type 1 (hiv-1). previously, we found that the mouse apobec3 (ma3) restricts infection by mouse mammary tumor virus (mmtv) in its natural host. dendritic cells (dcs) are the first in vivo targets of mmtv infection. in this study, we demonstrate that ma3 expressed in target cells restricts mmtv infection in dcs ex vivo and in vivo. by comparing infection of dcs fro ... | 2009 | 19153238 |
| role of a heterologous retroviral transport element in the development of genetic complementation assay for mouse mammary tumor virus (mmtv) replication. | the mouse mammary tumor virus (mmtv) is a type b retrovirus that is unique from other retroviruses in having multiple "tissue specific" and "hormone inducible" promoters. this unique feature has lead to the increasing interest in studying the biology of mmtv replication with the ultimate goal of developing mmtv based vectors for potentially targeted human gene therapy. in this report, we describe, for the first time, the establishment of an in vivo genetic complementation assay to study various ... | 2009 | 19157480 |
| mouse mammary tumour virus-like virus (mmtv-lv) is present within the liver in a wide range of hepatic disorders and unrelated to nuclear p53 expression or hepatocarcinogenesis. | the human equivalent of mouse mammary tumour virus (mmtv-lv) may have a role in the pathogenesis of primary biliary cirrhosis (pbc) and breast carcinogenesis. we investigated mmtv-lv prevalence in patients with liver disease of diverse aetiology and associations with hepatic expression of hormonal receptors, p53 protein and complicating hepatocarcinogenesis. | 2009 | 19168254 |
| the mpa mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer. | more than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (er) and progesterone receptors (pr). by contrast, most of the spontaneous, chemically or mouse mammary tumor virus induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. we developed a model of breast cancer in which the administration of medroxyprogesterone acetate to balb/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incide ... | 2009 | 19190078 |
| rev and rex proteins of human complex retroviruses function with the mmtv rem-responsive element. | mouse mammary tumor virus (mmtv) encodes the rem protein, an hiv rev-like protein that enhances nuclear export of unspliced viral rna in rodent cells. we have shown that rem is expressed from a doubly spliced rna, typical of complex retroviruses. several recent reports indicate that mmtv can infect human cells, suggesting that mmtv might interact with human retroviruses, such as human immunodeficiency virus (hiv), human t-cell leukemia virus (htlv), and human endogenous retrovirus type k (herv-k ... | 2009 | 19192308 |
| effects of selective sigma receptor ligands on glucocorticoid receptor-mediated gene transcription in lmcat cells. | it has been shown previously that sigma receptor agonists reveal potential antidepressant activity in experimental models. moreover, some data indicate sigma receptor contribution to stress-induced responses (e.g., conditioned fear stress in mice), though the mechanism by which sigma ligands can exert their effects, remains unclear. recent studies have indicated that antidepressant drugs (ads) inhibit glucocorticoid receptor (gr) function in vitro. the aim of the present study was to find out wh ... | 2008 | 19211981 |
| human endogenous retrovirus herv-k(hml-2) encodes a stable signal peptide with biological properties distinct from rec. | the human endogenous retrovirus herv-k(hml-2) family is associated with testicular germ cell tumors (gct). various hml-2 proviruses encode viral proteins such as env and rec. | 2009 | 19220907 |
| mmtv-wnt1 and -deltan89beta-catenin induce canonical signaling in distinct progenitors and differentially activate hedgehog signaling within mammary tumors. | canonical wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. a significant proportion of human breast cancer is associated with loss of secreted wnt antagonists and mice expressing mmtv-wnt1 and mmtv-deltan89beta-catenin develop mammary adenocarcinomas. many studies have assumed these mouse models of breast cancer to be equivalent. here we show that mmtv-wnt1 and mmtv-deltan89beta-catenin transgenes induce tumors with different phenotypes. ... | 2009 | 19225568 |
| cd93 is required for maintenance of antibody secretion and persistence of plasma cells in the bone marrow niche. | plasma cells represent the end stage of b-cell development and play a key role in providing an efficient antibody response, but they are also involved in numerous pathologies. here we show that cd93, a receptor expressed during early b-cell development, is reinduced during plasma-cell differentiation. high cd93/cd138 expression was restricted to antibody-secreting cells both in t-dependent and t-independent responses as naive, memory, and germinal-center b cells remained cd93-negative. cd93 was ... | 2009 | 19228948 |
| dna sequence-dependent variation in nucleosome structure, stability, and dynamics detected by a fret-based analysis. | förster resonance energy transfer (fret) techniques provide powerful and sensitive methods for the study of conformational features in biomolecules. here, we review fret-based studies of nucleosomes, focusing particularly on our work comparing the widely used nucleosome standard, 5s rdna, and 2 promoter-derived regulatory element-containing nucleosomes, mouse mammary tumor virus (mmtv)-b and gal10. using several fret approaches, we detected significant dna sequence-dependent structure, stability ... | 2009 | 19234544 |
| mouse mammary tumor virus: new tumor virus or just a rumor virus? | | 2009 | 19244171 |
| glucocorticoid receptor (gr) beta has intrinsic, gralpha-independent transcriptional activity. | the human glucocorticoid receptor (gr) gene produces c-terminal grbeta and gralpha isoforms through alternative use of specific exons 9beta and alpha, respectively. we explored the transcriptional activity of grbeta on endogenous genes by developing hela cells stably expressing egfp-grbeta or egfp. microarray analyses revealed that grbeta had intrinsic gene-specific transcriptional activity, regulating mrna expression of a large number of genes negatively or positively. majority of grbeta-respon ... | 2009 | 19248771 |
| combination therapy using three novel prolactin receptor antagonist-based fusion proteins effectively inhibits tumor recurrence and metastasis in her2/neu transgenic mice. | previously, prolactin receptor antagonist (g129r)- based fusion proteins were developed including g129r fusions with an angiogenesis inhibitor (endostatin), an immune system modulator (interleukin 2), and a modified truncated cytotoxin (pe38kdel). each fusion protein was designed to target the prlr-positive cells via the g129r moiety and at the same time attack a hallmark common to cancer cells via the second moiety. in this study, we tested the efficacy of the three fusion proteins as a combina ... | 2009 | 19287973 |
| ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation. | systemic hormones and local growth factor-mediated tissue interactions are essential for mammary gland development. using phenotypic and transplantation analyses of mice carrying the mesenchymal dysplasia (mes) allele of patched 1 (ptch1(mes)), we found that ptch1(mes) homozygosity led to either complete failure of gland development, failure of post-pubertal ductal elongation, or delayed growth with ductal dysplasia. all ductal phenotypes could be present in the same animal. whole gland and epit ... | 2009 | 19297414 |
| impaired lactation in mice expressing dominant-negative fadd in mammary epithelium. | the fas-associated death domain (fadd/mort1) adaptor protein was originally identified as a key mediator of apoptosis, although pleiotropic functions for fadd have also been reported. fadd-mediated tumoricidal effects have been described in breast cancer cells; however, its physiological role in normal mammary gland epithelium is not well understood. to determine the role of fadd signaling during mammary gland development, we generated transgenic mice overexpressing dominant-negative fadd (dn-fa ... | 2009 | 19301394 |
| adiponectin haploinsufficiency promotes mammary tumor development in mmtv-pyvt mice by modulation of phosphatase and tensin homolog activities. | adiponectin is an adipokine possessing beneficial effects on obesity-related medical complications. a negative association of adiponectin levels with breast cancer development has been demonstrated. however, the precise role of adiponectin deficiency in mammary carcinogenesis remains elusive. | 2009 | 19319191 |
| snake venom inhibits the growth of mouse mammary tumor cells in vitro and in vivo. | crude preparations as well as purified components of venoms isolated from american, asian and european snakes have been shown to inhibit the growth of some mouse and human cancer cell lines. however, it is not known if cerastes cerastes venom (ccv) obtained from the egyptian desert possesses any anti-tumor activity. in the present study we examined in vitro the effect of ccv on the growth rate and morphology of a mouse mammary tumor virus-induced mammary tumor cell line (riii/sa-mt). in addition ... | 2009 | 19327376 |
| mouse mammary tumor virus derived from wild mice does not target notch-4 protooncogene for the development of mammary tumors in inbred mice. | the colony of wild mice, named jyg, has been shown to express an exogenous mouse mammary tumor virus (jyg-mmtv). this virus induces mammary tumors in its natural host at a high incidence ( approximately 80%) resulting from insertion mutations in notch-4 (43%), wnt-1 (26%), and fgf-3 (13%). since the activation of notch-4 is not common in mammary tumors of standard laboratory strains of mice infected with various mmtv strains, we examined the consequences of jyg-mmtv infection in balb/c and c57bl ... | 2009 | 19329137 |
| infection of cells of human embryonal kidneys by mouse mammary tumor virus (mmtv). | | 2009 | 19341093 |
| impaired preadipocyte differentiation in human abdominal obesity: role of wnt, tumor necrosis factor-alpha, and inflammation. | we examined preadipocyte differentiation in obese and nonobese individuals and the effect of cytokines and wingless-type mmtv (mouse mammary tumor virus) integration site family, member 3a (wnt3a) protein on preadipocyte differentiation and phenotype. | 2009 | 19351711 |
| transcriptional regulation of estrogen receptor-alpha by p53 in human breast cancer cells. | estrogen receptor alpha (er) and p53 are critical prognostic indicators in breast cancer. loss of functional p53 is correlated with poor prognosis, er negativity, and resistance to antiestrogen treatment. previously, we found that p53 genotype was correlated with er expression and response to tamoxifen in mammary tumors arising in mouse mammary tumor virus-wnt-1 transgenic mice. these results lead us to hypothesize that p53 may regulate er expression. to test this, mcf-7 cells were treated with ... | 2009 | 19351845 |
| intrinsic promoter nucleosome stability/dynamics variations support a novel targeting mechanism. | genomic processes like transcription initiation typically involve the alteration of nucleosome structure, to expose dna elements for regulatory factor binding. nucleosome altering/modifying complexes have been identified, but precisely how these complexes find their specific targets remains unclear. we have shown that nucleosomes can exhibit significant dna sequence-dependent stability and dynamics variations and have suggested that these inherent variations could facilitate nucleosome recogniti ... | 2009 | 19374398 |
| the steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. | in breast cancer, steroid receptor coactivator-1 (src-1) expression positively correlates with her2 expression and poor prognosis. in mouse mammary tumor virus-polyoma middle t (pymt) breast cancer mouse model, src-1 strongly promotes mammary tumor metastasis. however, the molecular targets and mechanisms that mediate the role of src-1 in metastasis are unknown. in this study, src-1 wild-type (wt) and knockout (ko) cell lines were developed from the mammary tumors of wt/pymt and ko/pymt mice. wt ... | 2009 | 19383905 |
| bacillus anthracis lethal toxin represses mmtv promoter activity through transcription factors. | we have recently shown that the anthrax lethal toxin (letx) selectively represses nuclear hormone receptors. in this study, we found that letx repressed the activation of the mouse mammary tumor virus promoter related to overexpression of the transcription factors hepatocyte nuclear factor 3, octamer-binding protein 1, and c-jun. letx transcriptional repression was associated with a decrease in the protein levels of these transcription factors in a lethal factor protease activity-dependent manne ... | 2009 | 19389405 |
| mechanism of brca1-mediated inhibition of progesterone receptor transcriptional activity. | previously, we reported that brca1 inhibits progesterone receptor (pr) activity and blocks progesterone-stimulated gene expression and cell proliferation. in the present manuscript, we studied the mechanism of brca1 inhibition of pr activity, using c-myc as a model progesterone-regulated promoter. here, we found that brca1 has little or no effect on pr ligand-binding affinity. however, brca1 overexpression inhibited the r5020-induced recruitment of pr to the c-myc and mouse mammary tumor virus p ... | 2009 | 19389812 |
| interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis. | inflammation within the tumour microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. we have previously demonstrated that activation of a mouse mammary tumour virus (mmtv)-driven inducible fibroblast growth factor receptor 1 (ifgfr1) transgene in mammary epithelial cells results in an inflammatory response characterised by induction of inflammatory genes in the mammary gland. specifically, we have observed increased levels of ... | 2009 | 19393083 |
| abnormal mammary gland development in mmtv-cblc transgenic mouse. | the cbl family of e3 ubiquitin ligases regulates cell signaling in a number of tissues by promoting degradation of tyrosine kinase receptors such as epidermal growth factor receptor. cblc, the third member of the cbl family, is expressed in epithelial tissues, including the mammary gland. a transgenic mouse strain expressing a tetracyclin-inducible cblc in the mammary gland was derived. it was found that cblc transgene expression reduces the number and length of ducts during the development of t ... | 2009 | 19414407 |
| pten deficiency in a luminal erbb-2 mouse model results in dramatic acceleration of mammary tumorigenesis and metastasis. | overexpression and/or amplification of the erbb-2 oncogene as well as inactivation of the pten tumor suppressor are two important genetic events in human breast carcinogenesis. to address the biological impact of conditional inactivation of pten on erbb-2-induced mammary tumorigenesis, we generated a novel transgenic mouse model that utilizes the murine mammary tumor virus (mmtv) promoter to directly couple expression of activated erbb-2 and cre recombinase to the same mammary epithelial cell (m ... | 2009 | 19435886 |
| adiponectin deficiency limits tumor vascularization in the mmtv-pyv-mt mouse model of mammary cancer. | high levels of the fat-secreted cytokine adiponectin (apn) are present in the circulation of healthy people, whereas low levels correlate with an increased incidence of breast cancer in women. the current study experimentally probes the physiologic functions of apn in mammary cancer in a newly generated genetic mouse model. | 2009 | 19447866 |
| proangiogenic contribution of adiponectin toward mammary tumor growth in vivo. | adipocytes represent one of the most abundant constituents of the mammary gland. they are essential for mammary tumor growth and survival. metabolically, one of the more important fat-derived factors ("adipokines") is adiponectin (apn). serum concentrations of apn negatively correlate with body mass index and insulin resistance. to explore the association of apn with breast cancer and tumor angiogenesis, we took an in vivo approach aiming to study its role in the mouse mammary tumor virus (mmtv) ... | 2009 | 19447867 |
| myeloid-derived suppressor cells in mammary tumor progression in fvb neu transgenic mice. | female mice transgenic for the rat proto-oncogene c-erb-b2, under control of the mouse mammary tumor virus (mmtv) promoter (neun), spontaneously develop metastatic mammary carcinomas. the development of these mammary tumors is associated with increased number of gr-1(+)cd11b(+) myeloid derived suppressor cells (mdscs) in the peripheral blood (pb), spleen and tumor. we report a complex relationship between tumor growth, mdscs and immune regulatory molecules in non-mutated neu transgenic mice on a ... | 2010 | 19449184 |
| development of mammary tumors by conditional expression of gli1. | a diverse set of cellular defects, presumably elicited by multiple genetic alterations, underlies cancer development. aberrant hedgehog (hh) signaling has recently been implicated in the development and maintenance of breast cancer. however, evidence conclusively showing that activated hh signaling can induce mammary tumors is lacking. we now show that transgenic expression of the hh effector protein gli1 under the regulation of the mouse mammary tumor virus promoter, expressed in the mouse mamm ... | 2009 | 19458072 |
| histone acetylation characterizes chromatin presetting by nf1 and oct1 and enhances glucocorticoid receptor binding to the mmtv promoter. | transcription from the mouse mammary tumor virus (mmtv) promoter is induced by the glucocorticoid receptor (gr). this switch was reconstituted in xenopus oocytes. previously, we showed that nuclear factor 1 (nf1) and octamer transcription factor 1 (oct1) bind constitutively to the mmtv promoter and thereby induce translational nucleosome positioning representing an intermediary, i.e. preset, state of nucleosome organization. here we further characterize this nf1 and oct1 induced preset chromatin ... | 2009 | 19463811 |
| the canonical nf-kappab pathway is required for formation of luminal mammary neoplasias and is activated in the mammary progenitor population. | the role of the canonical nf-kappab pathway in mammary tumorigenesis was investigated using a transgenic (tg) mouse expressing a dominant-negative inhibitor of kappab (ikappabalpha(sr (s32a/s36a))) in the mammary gland under the control of the mouse mammary tumor virus promoter (mmtv). tg and control mice were subjected to a chemical carcinogenesis protocol. hyperkeratinized squamous metaplasias (cytokeratin-6+/p63+) sometimes with a basaloid island component, were found in both tg and control m ... | 2009 | 19483731 |
| akt1 and akt2 play distinct roles in the initiation and metastatic phases of mammary tumor progression. | the phosphatidylinositol 3-kinase (pi3k)/akt survival pathway is often dysregulated in cancer. our previous studies have shown that coexpression of activated akt1 with activated erbb2 or polyoma virus middle t antigen uncoupled from the pi3k pathway (pyvmt y315/322f) accelerates mammary tumor development but cannot rescue the metastatic phenotype associated with these models. here, we report the generation of transgenic mice expressing activated akt2 in the mammary epithelium. like the mouse mam ... | 2009 | 19491266 |
| the retroviral myth of primary biliary cirrhosis: is this (finally) the end of the story? | | 2009 | 19501424 |
| precision-cut slice cultures of tumors from mmtv-neu mice for the study of the ex vivo response to cytokines and cytotoxic drugs. | ex vivo analysis of signaling pathways operating in tumor tissue is complicated by the three-dimensional structure, in particular by stroma-epithelial interactions. studies performed with pure populations of tumor cells usually do not take into account this issue. one possibility to preserve the tissue architecture is the use of tumor slices. however, diffusion of oxygen and nutrients may become limiting factors, resulting in decreased cell viability and change of tissue morphology, especially a ... | 2009 | 19533258 |
| modulating the expression of ifn regulatory factor 8 alters the protumorigenic behavior of cd11b+gr-1+ myeloid cells. | cd11b(+)gr-1(+)-expressing cells, termed myeloid-derived suppressor cells, can mediate immunosuppression and tumor progression. however, the intrinsic molecular events that drive their protumorigenic behavior remain to be elucidated. although cd11b(+)gr-1(+) cells exist at low frequencies in normal mice, it also remains unresolved whether they are biologically distinct from those of tumor-bearing hosts. these objectives were investigated using cd11b(+)gr-1(+) cells from both implantable (4t1) an ... | 2009 | 19542426 |
| accelerated mammary maturation and differentiation, and delayed mmtvneu-induced tumorigenesis of k303r mutant eralpha transgenic mice. | we identified a somatic mutation in estrogen receptor-alpha (eralpha) in breast cancer causing a lysine to arginine transition (k303r) resulting in hypersensitivity to estrogen, altered associations with coactivators and corepressors and altered posttranslational modifications of eralpha. we have developed a transgenic mouse expressing the k303r mutant eralpha under control of the mouse mammary tumor virus (mmtv) promoter. at 4 months of age, k303r eralpha transgenic animals demonstrate precocio ... | 2009 | 19561644 |
| wnt antagonist gene polymorphisms and renal cancer. | epigenetic silencing of several wingless-type mouse mammary tumor virus integration site (wnt) pathway-related genes has been reported in renal cancer. except for the t-cell factor 4 gene tcf4, there are no reports regarding wnt pathway gene polymorphisms in renal cancer. therefore, the authors of this report hypothesized that the polymorphisms in wnt signaling genes may be risk factors for renal cancer. | 2009 | 19562778 |
| retroviral vectors containing tet-controlled bidirectional transcription units for simultaneous regulation of two gene activities. | in this study retroviral self-inactivating (sin)-vectors were constructed, that allow simultaneous regulation of two genes by integration of bidirectional tet controlled transcription units. marker genes (luciferase and egfp) were expressed under the control of various bidirectional promoters p(tet)bis, in order to determine (i) the fraction of htta-1 cells exhibiting tight doxycycline (dox) dependent control; (ii) possible effects of the vector backbone on the regulation of gene transcription; ... | 2006 | 19565004 |
| type i insulin-like growth factor receptor induces pulmonary tumorigenesis. | despite the type i insulin-like growth factor receptor (igf-ir) being highly expressed in more than 80% of human lung tumors, a transgenic model of igf-ir overexpression in the lung has not been created. we produced two novel transgenic mouse models in which igf-ir is overexpressed in either lung type ii alveolar cells (surfactant protein c [spc]-igfir) or clara cells (ccsp-igfir) in a doxycycline-inducible manner. overexpression of igf-ir in either cell type caused multifocal adenomatous alveol ... | 2009 | 19568412 |
| mmtv mouse models and the diagnostic values of mmtv-like sequences in human breast cancer. | mouse mammary tumor virus (mmtv) long terminal repeat (ltr)-driven transgenic mice are excellent models for breast cancer as they allow for the targeted expression of various oncogenes and growth factors in neoplastic transformation of mammary glands. numerous mmtv-ltr-driven transgenic mouse models of breast cancer have been created in the past three decades, including mmtv-neu/erbb2, cyclin d1, cyclin e, ras, myc, int-1 and c-rel. these transgenic mice develop mammary tumors with different lat ... | 2009 | 19580428 |
| the phylogeny of orthoretroviral long terminal repeats (ltrs). | ltrs are sequence elements in retroviruses and retrotransposons which are difficult to align due to their variability. one way of handling such cases is to use hidden markov models (hmms). in this work hmms of ltrs were constructed for three groups of orthoretroviruses: the betaretroviruslike human mmtv-like (hml) endogenous retroviruses, the lentiviruses, including hiv, and gammaretroviruslike human endogenous retroviruses (hervs). the hmm-generated ltr alignments and the phylogenetic trees con ... | 2009 | 19595747 |
| cross-packaging of genetically distinct mouse and primate retroviral rnas. | the mouse mammary tumor virus (mmtv) is unique from other retroviruses in having multiple viral promoters, which can be regulated by hormones in a tissue specific manner. this unique property has lead to increased interest in studying mmtv replication with the hope of developing mmtv based vectors for human gene therapy. however, it has recently been reported that related as well as unrelated retroviruses can cross-package each other's genome raising safety concerns towards the use of candidate ... | 2009 | 19602292 |
| met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. | elevated met receptor tyrosine kinase correlates with poor outcome in breast cancer, yet the reasons for this are poorly understood. we thus generated a transgenic mouse model targeting expression of an oncogenic met receptor (met(mt)) to the mammary epithelium. we show that met(mt) induces mammary tumors with multiple phenotypes. these reflect tumor subtypes with gene expression and immunostaining profiles sharing similarities to human basal and luminal breast cancers. within the basal subtype, ... | 2009 | 19617568 |
| the simultaneous induction of tumorigenesis and cre-loxp recombination in mice. | to investigate the role of rac1 for tumorigenesis, we generated inducible transgenic (tg) mice that simultaneously express polyomavirus middle t antigen (mt) and cre recombinase under the control of mouse mammary tumor virus long terminal repeat (mmtv-ltr) promoter (mmtv-ltr-tta/mt-tre-cre tg). mmtv-ltr-tta/mt- tre-cre tg mice formed tumors in the subcutaneous tissue and developed lung metastasis. we examined tumor latency and types in rac1 deficient (rac1(flox/-)) and control (rac1(+/+), rac1(+ ... | 2009 | 19628969 |
| mapping of the functional boundaries and secondary structure of the mouse mammary tumor virus rem-responsive element. | mouse mammary tumor virus (mmtv) is a complex retrovirus that encodes at least three regulatory and accessory proteins, including rem. rem is required for nuclear export of unspliced viral rna and efficient expression of viral proteins. our previous data indicated that sequences at the envelope-3' long terminal repeat junction are required for proper export of viral rna. to further map the rem-responsive element (rmre), reporter vectors containing various portions of the viral envelope gene and ... | 2009 | 19632991 |
| serum insulin-like growth factor-i and mammary tumor development in ad libitum-fed, chronic calorie-restricted, and intermittent calorie-restricted mmtv-tgf-alpha mice. | the effect of chronic (ccr) and intermittent (icr) caloric restriction on serum insulin-like growth factor (igf)-i levels and mammary tumor (mt) development was investigated. ten-week-old mmtv-tgf-alpha female mice were assigned to ad libitum-fed (al; ain-93m diet), icr [3-week 50% caloric restriction using ain-93m-mod diet, 2x protein, fat, vitamins, and minerals followed by 3 weeks of daily 100% al consumption of ain-93m ( approximately 75% of al for each 6-week cycle)], and ccr (calorie and n ... | 2009 | 19654106 |
| macronutrient intake and cancer: how does dietary restriction influence tumor growth and why should we care? | this perspective on the report by rogozina and colleagues (beginning on page 712 in this issue of the journal) reviews mechanisms that may underlie inhibitory effects of dietary restriction on tumor growth in the mouse mammary tumor virus transforming growth factor alpha (mmtv-tgf-alpha) breast cancer model and comments on the potential clinical relevance of these mechanisms. the inhibitory effect of caloric restriction on carcinogenesis and tumor growth in rodent models is a classic finding tha ... | 2009 | 19654107 |
| ligand activation of peroxisome proliferator-activated receptor-beta/delta (pparbeta/delta) inhibits cell growth in a mouse mammary gland cancer cell line. | the effects of ligand activation of pparbeta/delta were examined in the mouse mammary tumor cell line (c20). expression of pparbeta/delta was markedly lower in c20 cells as compared to the human non-tumorigenic mammary gland derived cell line (mcf10a) and mouse keratinocytes. ligand activation of pparbeta/delta in c20 cells caused upregulation of the pparbeta/delta target gene angiopoietin-like 4 (angptl4). inhibition of c20 cell proliferation and clonogenicity was observed following treatment w ... | 2010 | 19660859 |
| targeted overexpression of ezh2 in the mammary gland disrupts ductal morphogenesis and causes epithelial hyperplasia. | the polycomb group protein enhancer of zeste homolog 2 (ezh2), which has roles during development of numerous tissues, is a critical regulator of cell type identity. overexpression of ezh2 has been detected in invasive breast carcinoma tissue samples and is observed in human breast tissue samples of morphologically normal lobules up to 12 years before the development of breast cancer. the function of ezh2 during preneoplastic progression in the mammary gland is unknown. to investigate the role o ... | 2009 | 19661437 |
| cathepsin g-mediated activation of pro-matrix metalloproteinase 9 at the tumor-bone interface promotes transforming growth factor-beta signaling and bone destruction. | increased transforming growth factor-beta (tgf-beta) signaling has been observed at the tumor-bone interface of mammary tumor-induced osteolytic lesions despite no observed transcriptional up-regulation of tgf-beta. to this point, the mechanism for enhanced tgf-beta signaling remains unclear. the bulk of tgf-beta that is released at the tumor-bone interface is in an inactive form secondary to association with beta-latency-associated protein and latency tgf-beta binding protein. we hypothesized t ... | 2009 | 19671689 |
| foxa1 binding directs chromatin structure and the functional response of a glucocorticoid receptor-regulated promoter. | reconstitution of the glucocorticoid receptor (gr)-regulated mouse mammary tumor virus (mmtv) promoter in xenopus oocytes was used to monitor the effects of different transcription factor contexts. three constitutively binding factors, nuclear factor 1 (nf1), octamer transcription factor 1 (oct1), and the forkhead box a1 (foxa1), were shown to act in concert, to direct the chromatin structure, and to enhance the gr response. foxa1 has a dominant effect in the absence of hormone and induces a clu ... | 2009 | 19687299 |
| haploinsufficiency for p190b rhogap inhibits mmtv-neu tumor progression. | rho signaling regulates key cellular processes including proliferation, survival, and migration, and it has been implicated in the development of many types of cancer including breast cancer. p190b rho gtpase activating protein (rhogap) functions as a major inhibitor of the rho gtpases. p190b is required for mammary gland morphogenesis, and overexpression of p190b in the mammary gland induces hyperplastic lesions. hence, we hypothesized that p190b may play a pivotal role in mammary tumorigenesis ... | 2009 | 19703301 |
| disruption of histone modification and carm1 recruitment by arsenic represses transcription at glucocorticoid receptor-regulated promoters. | chronic exposure to inorganic arsenic (ias) found in the environment is one of the most significant and widespread environmental health risks in the u.s. and throughout the world. it is associated with a broad range of health effects from cancer to diabetes as well as reproductive and developmental anomalies. this diversity of diseases can also result from disruption of metabolic and other cellular processes regulated by steroid hormone receptors via aberrant transcriptional regulation. signific ... | 2009 | 19707557 |
| lessons in signaling and tumorigenesis from polyomavirus middle t antigen. | the small dna tumor viruses have provided a very long-lived source of insights into many aspects of the life cycle of eukaryotic cells. in recent years, the emphasis has been on cancer-related signaling. here we review murine polyomavirus middle t antigen, its mechanisms, and its downstream pathways of transformation. we concentrate on the mmtv-pymt transgenic mouse, one of the most studied models of breast cancer, which permits the examination of in situ tumor progression from hyperplasia to me ... | 2009 | 19721090 |
| parathyroid hormone-related protein protects against mammary tumor emergence and is associated with monocyte infiltration in ductal carcinoma in situ. | parathyroid hormone-related protein (pthrp) is required for mammary gland development and promotes the growth of breast cancer metastases within bone. however, there are conflicting reports of the prognostic significance of its expression in primary breast cancers. to study the role of pthrp in early breast cancer, the effect of conditional deletion of pthrp was examined in the context of neu-induced mammary tumorigenesis. loss of pthrp resulted in a higher tumor incidence. transcriptional profi ... | 2009 | 19723659 |
| nedd9 promotes oncogenic signaling in mammary tumor development. | in the past 3 years, altered expression of the hef1/cas-l/nedd9 scaffolding protein has emerged as contributing to cancer metastasis in multiple cancer types. however, whereas some studies have identified elevated nedd9 expression as prometastatic, other work has suggested a negative role in tumor progression. we here show that the nedd9-null genetic background significantly limits mammary tumor initiation in the mmtv-polyoma virus middle t genetic model. action of nedd9 is tumor cell intrinsic, ... | 2009 | 19738060 |
| mouse mammary tumor virus p75 and p110 cux1 transgenic mice develop mammary tumors of various histologic types. | the p75 and p110 isoforms of the cux1 homeodomain protein are overexpressed in breast tumors and cancer cell lines. to assess and compare the ability of these short cux1 isoforms in driving mammary tumor development, we used site-specific transgenesis into the hprt locus to generate transgenic mice expressing p75 or p110 cux1 under the control of the mouse mammary tumor virus-long terminal repeat. we report that mammary tumors developed after a long latency period, and although various histopath ... | 2009 | 19738070 |
| recognition imaging of acetylated chromatin using a dna aptamer. | histone acetylation plays an important role in the regulation of gene expression. a dna aptamer generated by in vitro selection to be highly specific for histone h4 protein acetylated at lysine 16 was used as a recognition element for atomic force microscopy-based recognition imaging of synthetic nucleosomal arrays with precisely controlled acetylation. the aptamer proved to be reasonably specific at recognizing acetylated histones, with recognition efficiencies of 60% on-target and 12% off-targ ... | 2009 | 19751687 |
| jaagsiekte sheep retrovirus encodes a regulatory factor, rej, required for synthesis of gag protein. | retroviruses express gag and pol proteins by translation of unspliced genome-length viral rna. for some retroviruses, transport of unspliced viral rna to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus rev, while other retroviruses contain constitutive transport elements in their rnas that allow transport without splicing. in this study, we found that the betaretrovirus jaagsiekte sheep retrovirus (jsrv) encodes within the env gene a trans-acting facto ... | 2009 | 19776124 |
| a novel isoform of human lzip negatively regulates the transactivation of the glucocorticoid receptor. | the human leucine zipper protein (lzip) is a basic leucine zipper transcription factor that is involved in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. although evidence suggests a diversity of roles for lzip, its function is not fully understood, and the subcellular localization of lzip is still controversial. we identified a novel isoform of lzip and characterized its function in ligand-induced transactivation of the glucocorticoid re ... | 2009 | 19779205 |
| detection of human mammary tumor virus proteins in human breast cancer cells. | mouse mammary tumor virus (mmtv) has been proven to induce mammary cancer in mice. mmtv-like env gene sequences have been detected in one-third of the human breast tumors studied. the whole proviral structure with 95% homology to mmtv was found in two human breast tumors and was designated as human mammary tumor virus (hmtv). hmtv viral particles with betaretroviral features have been isolated. in addition, a retrovirus called human betaretrovirus (hbrv), homologous to the mentioned retroviruses ... | 2010 | 19781575 |
| myosin vi is a modulator of androgen-dependent gene expression. | myosin vi, one of the so-called unconventional myosins, is an actin-based molecular motor involved in intracellular vesicle and organelle transport. in human prostate, myosin vi is expressed in prostate epithelium. we examined the effect of myosin vi downregulation in the lncap human prostate cancer cell line using an rna interference approach. further, the expression of myosin vi in human prostate tissue was examined using immunohistochemistry. the expression of androgen receptor (ar) and e-cad ... | 2009 | 19787211 |
| assembly mechanisms of rna pseudoknots are determined by the stabilities of constituent secondary structures. | understanding how rna molecules navigate their rugged folding landscapes holds the key to describing their roles in a variety of cellular functions. to dissect rna folding at the molecular level, we performed simulations of three pseudoknots (mmtv and srv-1 from viral genomes and the htr pseudoknot from human telomerase) using coarse-grained models. the melting temperatures from the specific heat profiles are in good agreement with the available experimental data for mmtv and htr. the equilibriu ... | 2009 | 19805055 |
| direct and indirect contribution of bone marrow-derived cells to cancer. | stromal-epithelial interactions may control the growth and initiation of cancers. here, we not only test the hypothesis that bone marrow-derived cells may effect development of cancers arising from other tissue cells by forming tumor stroma but also that sarcomas may arise by transformation of stem cells from the bone marrow and epithelial cancers may arise by transdifferentiation of bone marrow stem cells to epithelial cancers. lethally irradiated female fvb/n mice were restored with bone marro ... | 2010 | 19816927 |
| smad1-smad5 ovarian conditional knockout mice develop a disease profile similar to the juvenile form of human granulosa cell tumors. | granulosa cell tumors (gcts) of the ovary are rare sex cord stromal tumors. although generally indolent, gcts recur, and if not diagnosed and treated in early stages, survival rates are significantly shortened. very little is known regarding gct etiology. because of the low incidence of cases and lack of standard diagnostics, mouse models for granulosa cell tumors are a valuable tool for studying gcts and provide models for developing diagnostic and treatment strategies. we recently developed a ... | 2009 | 19819941 |
| therapeutic activity of sunitinib for her2/neu induced mammary cancer in fvb mice. | mouse mammary tumor virus-neu (mmtv/neu) transgenic mice on an fvb-background (fvb-neun) have increased numbers of myeloid derived suppressor cells (mdscs) and regulatory t-cells (t-regs) in the spleen during mammary tumor induction and progression. using this transgenic tumor model, we assessed the therapeutic activity of sunitinib, a multi-targeted, tyrosine kinase (tk) inhibitor and its effects on immune-regulatory cells. our preliminary results show that sunitinib at 40mg/kg/day, p.o. (per o ... | 2010 | 19833232 |
| identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands. | androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. selective androgen receptor modulators (sarms) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. we describe two structurally similar 4-aza-steroidal androgen receptor (ar) ligands, cl-4as-1, a full agonist, and tfm-4as-1, which is a sarm. tfm ... | 2009 | 19846549 |
| evidence for a tumor promoting effect of high-fat diet independent of insulin resistance in her2/neu mammary carcinogenesis. | the mechanism of the association between breast cancer and obesity remains unknown. to investigate this mice over-expressing her2/neu in the mammary gland (mmtv-her2/neu) were fed either a high-fat diet (45% of calories) (hfd) or low-fat diet (10%) (lfd) from 4 weeks of age and followed for up to 1 year, or sacrificed when a mammary tumor reached 1.5 cm. there was a small but significant increase in body weight on hfd (p < 0.05) and the hfd mice displayed a greater fat mass determined by mri (p ... | 2010 | 19851863 |
| wnt signaling activation and mammary gland hyperplasia in mmtv-lrp6 transgenic mice: implication for breast cancer tumorigenesis. | although wnt signaling activation is frequently observed in human breast cancer, mutations in genes encoding intracellular components of the wnt signaling pathway are rare. we found that the expression of wnt signaling co-receptor, lrp6, is upregulated in a subset of human breast cancer tissues and cell lines. to examine whether the overexpression of lrp6 in mammary epithelial cells is sufficient to activate wnt signaling and promote cell proliferation, we generated transgenic mice overexpressin ... | 2010 | 19881541 |
| the 5'-untranslated region of the mouse mammary tumor virus mrna exhibits cap-independent translation initiation. | in this study, we demonstrate the identification of an internal ribosome entry site (ires) within the 5'-untranslated region (5'-utr) of the mouse mammary tumor virus (mmtv). the 5'-utr of the full-length mrna derived from the infectious, complete mmtv genome was cloned into a dual luciferase reporter construct containing an upstream renilla luciferase gene (rluc) and a downstream firefly luciferase gene (fluc). in rabbit reticulocyte lysate, the mmtv 5'-utr was capable of driving translation of ... | 2010 | 19889724 |
| regulation of wingless-type mmtv integration site family (wnt) signalling in pancreatic islets from wild-type and obese mice. | tcf7l2 is a type 2 diabetes susceptibility gene and downstream effector of canonical wingless-type mmtv integration site family (wnt) signalling. however, it is unknown whether this pathway is active in adult pancreatic islets in vivo, and whether it is regulated in obesity. | 2010 | 19898815 |
| optical imaging of the peri-tumoral inflammatory response in breast cancer. | peri-tumoral inflammation is a common tumor response that plays a central role in tumor invasion and metastasis, and inflammatory cell recruitment is essential to this process. the purpose of this study was to determine whether injected fluorescently-labeled monocytes accumulate within murine breast tumors and are visible with optical imaging. | 2009 | 19906309 |
| divergent human remodeling complexes remove nucleosomes from strong positioning sequences. | nucleosome positioning plays a major role in controlling the accessibility of dna to transcription factors and other nuclear processes. nucleosome positions after assembly are at least partially determined by the relative affinity of dna sequences for the histone octamer. nucleosomes can be moved, however, by a class of atp dependent chromatin remodeling complexes. we recently showed that the human swi/snf remodeling complex moves nucleosomes in a sequence specific manner, away from nucleosome p ... | 2010 | 19906705 |
| prevention of mammary carcinogenesis in mmtv-neu mice by cruciferous vegetable constituent benzyl isothiocyanate. | benzyl isothiocyanate (bitc), a constituent of edible cruciferous vegetables, inhibits growth of human breast cancer cells in culture. the present study provides in vivo evidence for efficacy of bitc for prevention of mammary cancer in mmtv-neu mice. administration of bitc at 1 and 3 mmol/kg diet for 25 weeks markedly suppressed the incidence and/or burden of mammary hyperplasia and carcinoma in female mmtv-neu mice without causing weight loss or affecting neu protein level. for example, cumulat ... | 2009 | 19934325 |
| nuclear factor 1 synergizes with progesterone receptor on the mouse mammary tumor virus promoter wrapped around a histone h3/h4 tetramer by facilitating access to the central hormone-responsive elements. | steroid hormones induce transcription of their responsive genes by complex mechanisms including synergism between the hormone receptors and other transcription factors. on the mouse mammary tumor virus (mmtv) promoter progesterone induction is mediated by the reciprocal synergism between progesterone receptor (pr) and the ubiquitous transcription factor nuclear factor 1 (nf1). pr binding mediates atp-dependent displacement of histone h2a and h2b, enabling nf1 access to its target site. in minich ... | 2010 | 19940123 |
| upregulation of neutrophil gelatinase-associated lipocalin by erbb2 through nuclear factor-kappab activation. | erbb2 (her2, neu) is a receptor tyrosine kinase overexpressed in about 25% of invasive breast carcinomas. neutrophil gelatinase-associated lipocalin (ngal) is a secreted glycoprotein expressed in a variety of cancers, including breast carcinomas. ngal can inhibit erythroid cell production, leading to anemia. anemia usually occurs in cancer patients and negatively affects quality of life. however, current treatment for cancer-related anemia has potential complications. erbb2, ngal, and anemia hav ... | 2009 | 19951994 |
| junctional diversity prevents negative selection of an antigen-specific t cell repertoire. | endogenous mouse mammary tumor proviruses (mmtv; mtv loci) deletes vbeta6 expressing t cells in the thymus of mtv-7(+) dba/2 (h2(d)) mice through negative selection. we found that in mtv-7(-) balb/c (h2(d)) mice, vbeta6 is a dominant v gene used in t cell responses to an 18 amino acid long peptide antigen: eykeyaeyaeyaeyaeya [abbreviated as k5 or eyk(eya)(5)]. it was therefore surprising to find that despite the deletion of vbeta6+ t cells, vigorous k5 specific t cell responses that use vbeta6 c ... | 2010 | 19954850 |
| protein expression profiling of primary mammary epithelial cells derived from mmtv-neu mice revealed that her2/neu-driven changes in protein expression are functionally clustered. | mmtv-neu transgenic mice overexpressing neu in their mammary glands develop tumor after 6 months of age. to find a novel protein biomarker using this mouse model, we identified and characterized the proteins that were differently expressed between primary mammary epithelial cells from 2 months old mmtv-neu heterozygote mice and wild type (wt) littermates using two-dimensional digest (chemdigest/trypsin)-lc-ms/ms. the differentially expressed proteins were selected and analyzed using david bioinf ... | 2010 | 19960538 |
| crkii transgene induces atypical mammary gland development and tumorigenesis. | the v-crk protein was originally isolated as the oncogene fusion product of the ct10 chicken retrovirus. cellular homologues of v-crk include crk, which encodes two alternatively spliced proteins (crki and crkii), and crkl. though crki/ii proteins are elevated in several types of cancer, including breast, the question of whether these crk adaptor proteins can promote breast cancer has not been addressed. we created a transgenic mouse model that allows the expression of crkii through the hormonal ... | 2010 | 20008144 |
| imaging spontaneous mmtvneu transgenic murine mammary tumors: targeting metabolic activity versus genetic products. | despite the great strides made in imaging breast cancer (bc) in humans, the current imaging modalities miss up to 30% of bc, do not distinguish malignant lesions from benign ones, and require histologic examinations for which invasive biopsy must be performed. annually in the united states, approximately 5.6 million biopsies find benign lesions. more than 50% of human bcs overexpress cyclin d1, and all bcs exhibit vpac1 oncogene products. together, these gene products may provide an excellent bi ... | 2010 | 20008985 |
| in vivo characterization of activatable cell penetrating peptides for targeting protease activity in cancer. | activatable cell penetrating peptides (acpps) are novel in vivo targeting agents comprised of a polycationic cell penetrating peptide (cpp) connected via a cleavable linker to a neutralizing polyanion (). adsorption and uptake into cells are inhibited until the linker is proteolyzed. an acpp cleavable by matrix metalloproteinase-2 (mmp-2) in vitro was the first one demonstrated to work in a tumor model in vivo, but only ht-1080 xenografts and resected human squamous cell carcinomas were tested. ... | 2009 | 20023745 |
| glucocorticoid receptor phosphorylation modulates transcription efficacy through grip-1 recruitment. | the role of gr phosphorylation in modulating gr-mediated transcription is not fully understood. here we show that the hgr is rapidly phosphorylated at s211 and s226 in response to the synthetic agonist dexamethasone (dex) in cos-1 cells. using a triple phosphorylation mutant hgr construct, we demonstrate that phosphorylation at one or more s residues (from s203, s211, and s226) is required for maximal hgr-mediated transcriptional activation on the mmtv promoter in response to dex in cos-1 cells, ... | 2010 | 20047289 |
| targeted production of proprotein convertase pc1 enhances mammary development and tumorigenesis in transgenic mice. | elevated production of proprotein convertases (pcs), proteolytic enzymes that posttranslationally modify the biological activities of diverse groups of cellular proteins, is a common occurrence in human breast carcinomas. a transgenic mouse model was developed to gain insight into the significance of pc production in breast development and neoplasia. mammary epithelium-specific and early expression of pc1 was targeted by the use of the mouse mammary tumor virus promoter/enhancer. whole-mount exa ... | 2009 | 20052009 |
| stromal cell-derived factor-1/cxcl12 contributes to mmtv-wnt1 tumor growth involving gr1+cd11b+ cells. | histological examinations of mmtv-wnt1 tumors reveal drastic differences in the tumor vasculature when compared to mmtv-her2 tumors. however, these differences have not been formally described, nor have any angiogenic factors been implicated to be involved in the wnt1 tumors. | 2010 | 20087418 |
| erk signaling and chromatin remodeling in mmtv promoter activation by progestins. | transcription from the mouse mammary tumor virus (mmtv) promoter can be induced by progestins. the progesterone receptor (pr) binds to a cluster of five hormone responsive elements (hres) and activates the promoter by synergistic interactions with the ubiquitous transcription factor, nuclear factor 1 (nf1). progesterone treatment of cells in culture leads to activation of the src/ras/erk/msk1 cascade. selective inhibition of erk, or its target kinase msk1, interferes with chromatin remodeling an ... | 2009 | 20087429 |
| a role for kai1 in promotion of cell proliferation and mammary gland hyperplasia by the gp78 ubiquitin ligase. | expression of gp78, an e3 ubiquitin ligase in endoplasmic reticulum-associated degradation, is associated with tumor malignancy. to study gp78 overexpression in mammary gland development and tumorigenicity, we generated murine mammary tumor virus (mmtv) long terminal repeat-driven gp78 transgenic mice. embryos carrying the gp78 transgene cassette were implanted in fvb surrogate mothers, and two founders with high copy integration showed elevated gp78 expression at both transcript and protein lev ... | 2010 | 20089858 |
| lung metastasis fails in mmtv-pymt oncomice lacking s100a4 due to a t-cell deficiency in primary tumors. | interactions between tumor and stroma cells are essential for the progression of cancer from its initial growth at a primary site to its metastasis to distant organs. the metastasis-stimulating protein s100a4 exerts its function as a stroma cell-derived factor. genetic depletion of s100a4 significantly reduced the metastatic burden in lungs of pymt-induced mammary tumors. in s100a4(+/+) pymt mice, massive leukocyte infiltration at the site of the growing tumor at the stage of malignant transitio ... | 2010 | 20103644 |
| cyclooxygenase-2 inhibition for the prophylaxis and treatment of preinvasive breast cancer in a her-2/neu mouse model. | ductal carcinoma in situ (dcis) is the most common form of preinvasive breast cancer. several molecular alterations have been identified in dcis. among them, cyclooxygenase 2 (cox-2) overexpression has been shown in 60% to 80% of dcis cases. celecoxib is a nonsteroidal anti-inflammatory drug that selectively inhibits cox-2. in this study, we evaluated whether cox-2 inhibition by celecoxib can reduce the incidence of preinvasive breast cancer and its progression to invasive breast cancer in a mou ... | 2010 | 20103725 |
| pea3 transcription factors and wnt1-induced mouse mammary neoplasia. | the role of the pea3 subfamily of ets transcription factors in breast neoplasia is controversial. although overexpression of pea3 (e1af/etv4), and of the related factors erm (etv5) and er81 (etv1), have been observed in human and mouse breast tumors, pea3 factors have also been ascribed a tumor suppressor function. here, we utilized the mmtv/wnt1 mouse strain to further interrogate the role of pea3 transcription factors in mammary tumorigenesis based on our previous observation that pea3 is high ... | 2010 | 20107508 |