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anti-androgenic activity of hydroxyxanthones in prostate cancer lncap cells.anti-androgens are used to treat prostate cancer. here, we report that hydroxyxanthones from a plant extract act as anti-androgens in androgen receptor (ar)-positive prostate cancer lncap cells. anti-androgenic activity of the ethanol extract from garcinia subelliptica was observed in a luciferase assay using lncap/mmtv cells with a stably integrated mouse mammary tumor virus (mmtv) promoter. hplc-based activity profiling followed by a chemical library-based assay strategy enabled the rapid iden ...201424084319
protein kinase cδ is required for erbb2-driven mammary gland tumorigenesis and negatively correlates with prognosis in human breast cancer.protein kinase c δ (pkcδ) regulates apoptosis in the mammary gland, however, the functional contribution of pkcδ to the development or progression of breast cancer has yet to be determined. meta-analysis of erbb2-positive breast cancers shows increased pkcδ expression, and a negative correlation between pkcδ expression and prognosis. here, we present in-vivo evidence that pkcδ is essential for the development of mammary gland tumors in a erbb2-overexpressing transgenic mouse model, and in-vitro ...201423474764
runx2 correlates with subtype-specific breast cancer in a human tissue microarray, and ectopic expression of runx2 perturbs differentiation in the mouse mammary gland.runx2, a master regulator of osteogenesis, is oncogenic in the lymphoid lineage; however, little is known about its role in epithelial cancers. upregulation of runx2 in cell lines correlates with increased invasiveness and the capacity to form osteolytic disease in models of breast and prostate cancer. however, most studies have analysed the effects of this gene in a limited number of cell lines and its role in primary breast cancer has not been resolved. using a human tumour tissue microarray, ...201424626992
the research progress of the interactions between mirna and wnt/beta-catenin signaling pathway in breast cancer of human and mice .microrna expression is a research focus in studies of tumors. this article concentrates attention on potential links between tumors caused by mouse mammary tumor virus (mmtv) and human breast cancer, in order to provide theoretical basis for using mouse model to search for mirna effects mediated by wnt/beta-catenin signaling in human breast cancer. by analyzing interactions between mirnas and the wnt/beta-catenin signaling pathway in breast cancer, we hope to casts light on more biological funct ...201424606421
balanced duo of anti-inflammatory sfrp5 and proinflammatory wnt5a in children.secreted frizzled-related protein 5 (sfrp5) is an adipokine protecting against obesity-related insulin resistance and diabetes. sfrp5 binds to wingless type mouse mammary tumor virus (mmtv) integration site family member 5a (wnt5a) to improve insulin sensitivity. we performed the first study of sfrp5 and wnt5a simultaneously in children.201424603290
ezh2 expands breast stem cells through activation of notch1 signaling.breast cancer is the second-leading cause of cancer-related deaths in women, but the details of how it begins remain elusive. increasing evidence supports the association of aggressive triple-negative (tn) breast cancer with heightened expression of the polycomb group protein enhancer of zeste homolog 2 (ezh2) and increased tumor-initiating cells (tics). however, mechanistic links between ezh2 and tics are unclear, and direct demonstration of a tumorigenic function of ezh2 in vivo is lacking. he ...201424516139
a murine retrovirus co-opts yb-1, a translational regulator and stress granule-associated protein, to facilitate virus assembly.the gag protein of the murine retrovirus mouse mammary tumor virus (mmtv) orchestrates the assembly of immature virus particles in the cytoplasm which are subsequently transported to the plasma membrane for release from the cell. the morphogenetic pathway of mmtv assembly is similar to that of saccharomyces cerevisiae retrotransposons ty1 and ty3, which assemble virus-like particles (vlps) in intracytoplasmic ribonucleoprotein (rnp) complexes. assembly of ty1 and ty3 vlps depends upon cellular m ...201424501406
a novel point mutation of the human glucocorticoid receptor gene causes primary generalized glucocorticoid resistance through impaired interaction with the lxxll motif of the p160 coactivators: dissociation of the transactivating and transreppressive activities.primary generalized glucocorticoid resistance is a rare genetic disorder characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. the molecular basis of the condition has been ascribed to inactivating mutations in the human glucocorticoid receptor (hgr) gene.201424483153
canonical wnt signaling inhibits follicle stimulating hormone mediated steroidogenesis in primary cultures of rat granulosa cells.beta-catenin (ctnnb1), a key component of wingless-type mouse mammary tumor virus integration site family (wnt) signaling, participates in follicle stimulated hormone-mediated regulation of estrogen (e2) production. the purpose of these studies was to determine if ctnnb1's contribution to fsh-mediated steroidogenesis in primary rat granulosa cells was due in part to extracellular stimulation of the canonical wnt signaling pathway. to achieve this purpose, primary cultures of rat granulosa cells ...201424466091
inducible and coupled expression of the polyomavirus middle t antigen and cre recombinase in transgenic mice: an in vivo model for synthetic viability in mammary tumour progression.effective in vivo models of breast cancer are crucial for studying the development and progression of the disease in humans. we sought to engineer a novel mouse model of polyomavirus middle t antigen (pyv mt)-mediated mammary tumourigenesis in which inducible expression of this well-characterized viral oncoprotein is coupled to cre recombinase (teto-pyv mt-ires-cre recombinase or mic).201424457046
mmtv superantigens coerce an unconventional topology between the tcr and mhc class ii.mouse mammary tumor virus superantigens (vsags) are notorious for defying structural characterization, and a consensus has yet to be reached regarding their ability to bridge the tcr to mhc class ii (mhcii). in this study, we determined the topology of the t cell signaling complex by examining the respective relation of vsag7 with the mhcii molecule, mhcii-associated peptide, and tcr. we used covalently linked peptide/mhcii complexes to demonstrate that vsag presentation is tolerant to variation ...201424453254
detection of mmtv-like sequences in moroccan breast cancer cases.the mouse mammary tumor virus (mmtv) like sequences have been reported to be present in some human breast cancers, but their association with breast cancer development is still controversial.201425926863
aquaporin-1 gene deletion reduces breast tumor growth and lung metastasis in tumor-producing mmtv-pyvt mice.aquaporin 1 (aqp1) is a plasma membrane water-transporting protein expressed strongly in tumor microvascular endothelia. we previously reported impaired angiogenesis in implanted tumors in aqp1-deficient mice and reduced migration of aqp1-deficient endothelial cells in vitro. here, we investigated the consequences of aqp1 deficiency in mice that spontaneously develop well-differentiated, luminal-type breast adenomas with lung metastases [mouse mammary tumor virus-driven polyoma virus middle t on ...201424334548
eph receptor and ephrin function in breast, gut, and skin epithelia.epithelial cells are tightly coupled together through specialized intercellular junctions, including adherens junctions, desmosomes, tight junctions, and gap junctions. a growing body of evidence suggests epithelial cells also directly exchange information at cell-cell contacts via the eph family of receptor tyrosine kinases and their membrane-associated ephrin ligands. ligand-dependent and -independent signaling via eph receptors as well as reverse signaling through ephrins impact epithelial ti ...201425482622
modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis.spot14 (s14), encoded by the thrsp gene, regulates de novo fatty acid synthesis in the liver, adipose, and lactating mammary gland. we recently showed that s14 stimulated fatty acid synthase (fasn) activity in vitro, and increased the synthesis of fatty acids in mammary epithelial cells in vivo. elevated de novo fatty acid synthesis is a distinguishing feature of many solid tumors compared with adjacent normal tissue. this characteristic is thought to be acquired during tumor progression, as rap ...201425472762
inactivation of rarβ inhibits wnt1-induced mammary tumorigenesis by suppressing epithelial-mesenchymal transitions.retinoic acid receptor β (rarβ) has been proposed to act as a tumor suppressor in breast cancer. in contrast, recent data have shown that rarβ promotes erbb2-induced mammary gland tumorigenesis through remodeling of the stromal compartment and activation of cancer-associated fibroblasts. however, it is currently unknown whether rarβ oncogenic activity is specific to erbb2-induced tumors, or whether it influences the initiation and progression of other breast cancer subtypes. accordingly, we set ...201425422594
structural basis of genomic rna (grna) dimerization and packaging determinants of mouse mammary tumor virus (mmtv).one of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral grna in the form of a non-covalent rna dimer by the assembling virions. it is becoming increasingly clear that the process of dimerization is closely linked with grna packaging, and in some retroviruses, the latter depends on the former. earlier mutational analysis of the 5' end of the mmtv genome indicated that mmtv grna packaging determinants comprise sequences both within the 5' u ...201425394412
intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations.tumor-infiltrating inflammatory cells comprise a major part of the stromal microenvironment and support cancer progression by multiple mechanisms. high numbers of tumor myeloid cells correlate with poor prognosis in breast cancer and are coupled with the angiogenic switch and malignant progression. however, the specific roles and regulation of heterogeneous tumor myeloid populations are incompletely understood. csf-1 is a major myeloid cell mitogen, and signaling through its receptor csf-1r is a ...201425385645
fli1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression.ets factors have been shown to be dysregulated in breast cancer. ets factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. fli1 is an ets protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of fli1 in epithelial-derived cancers. using data mining, we show that loss of fli1 expression is associated with shorter survival ...201425379017
autophagy regulator becn1 suppresses mammary tumorigenesis driven by wnt1 activation and following parity.earlier studies reported allelic deletion of the essential autophagy regulator becn1 in breast cancers implicating becn1 loss, and likely defective autophagy, in tumorigenesis. recent studies have questioned the tumor suppressive role of autophagy, as autophagy-related gene (atg) defects generally suppress tumorigenesis in well-characterized mouse tumor models. we now report that, while it delays or does not alter mammary tumorigenesis driven by palb2 loss or erbb2 and pymt overexpression, monoa ...201425483966
luteolin supplementation modulates mammary tumor growth in c3h mice fed diet with high- and low-fat content.in this study we investigated the effects of luteolin supplementation (0.05% w/w) on mammary tumor growth in c3h mice, a strain of mouse mammary tumor virus negative, fed either high-fat (45% fat of energy) or low-fat diet (15% fat of energy). animals (n = 12/group) were allocated into 4 experimental groups (low-fat diet, low-fat diet + luteolin supplementation, high-fat diet, high-fat diet + luteolin supplementation). experimental diet were fed for 13 wk and 7,12-dimethylbenz[a]anthracene was a ...201424074002
new perspectives on β-catenin control of cell fate and proliferation in colon cancer.colorectal cancer is a major health problem worldwide. aberrant activation of the wingless-type mouse mammary tumor virus integration site family(wnt)/β-catenin signaling pathway is the most common and initial alteration in sporadic colorectal tumors. numerous experimental studies have indicated that β-catenin is a key regulator of colorectal cancer. indeed, β-catenin activity was shown to designate colon cancer stem cells (csc) and is, therefore, an attractive target for new therapeutic agents. ...201425193262
[generation and comparison of two genetically engineered mouse models of erbb2/neu positive-pten deficient breast cancer].to generate two genetically engineered mouse models of erbb2/neu positive-pten deficient breast cancer and to compare their biological properties.201425187457
human mammary tumor virus (hmtv) sequences in human milk.retroviral sequences 90-95% homologous to the mouse mammary tumor virus (mmtv) were present in 38% of the breast cancers studied from american women and were not detectable in non-tumor breast tissue from the same patient. the entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. this virus was designated as human mammary tumor virus (hmtv). hormone response elements present in the hmtv long-terminal-repeat (ltr) suggest a mechani ...201425120582
the distribution of insertionally polymorphic endogenous retroviruses in breast cancer patients and cancer-free controls.integration of retroviral dna into a germ cell can result in a provirus that is transmitted vertically to the host's offspring. in humans, such endogenous retroviruses (hervs) comprise >8% of the genome. the herv-k(hml-2) proviruses consist of ~90 elements related to mouse mammary tumor virus, which causes breast cancer in mice. a subset of herv-k(hml-2) proviruses has some or all genes intact, and even encodes functional proteins, though a replication competent copy has yet to be observed. more ...201425112280
estrogen receptor inhibits mineralocorticoid receptor transcriptional regulatory function.the steroid hormone aldosterone (aldo) contributes to cardiovascular disease in animal models and in humans. aldo activates the mineralocorticoid receptor (mr), a hormone-activated transcription factor, and indeed, pharmacological mr inhibition improves cardiovascular outcomes. because the incidence of cardiovascular disease is lower in premenopausal women, we hypothesized that estrogen (e2) signaling through the estrogen receptor (er) may protect the vasculature by inhibiting the detrimental ef ...201425051445
wnt16b from ovarian fibroblasts induces differentiation of regulatory t cells through β-catenin signal in dendritic cells.treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. wingless-type mmtv (mouse mammary tumor virus) integration site 16b (wnt16b) is a new member of the wnt family and has been reported to play growth-related roles in previous studies. in this study, we found wnt16b could be expressed and secreted into the microenvironment by human ovarian fibroblasts after dna damage-associated treatment, including chemotherapy drugs ...201425050785
deletion of cd151 reduces mammary tumorigenesis in the mmtv/pymt mouse model.tetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling. cd151 is part of the tetraspanin family and it forms tight complexes with β1 and β4 integrins, both of which have been shown to be required for tumorigenesis and/or metastasis in transgenic mouse models of breast cancer. high levels of ...201425012362
challenging role of wnt5a and its signaling pathway in cancer metastasis (review).wnt5a is a noncanonical signaling member of the wingless-related/mouse mammary tumor virus integration family, which is involved in a wide range of cellular processes, particularly in cancer development and metastasis. accumulating evidence indicates that wnt5a exhibits paradoxical effects in various types of cancer metastasis. therefore, the wnt5a signaling cascade in cancer metastasis appears to be complex and may depend on binding receptors, downstream effectors, exogenous inhibitors and tumo ...201424944588
mouse mammary tumor virus-like virus infection and the risk of human breast cancer: a meta-analysis.despite a large number of molecular epidemiological studies, the association of mouse mammary tumor virus-like virus (mmtv-lv) infection with the risk of human breast cancer remains inconclusive mainly due to the heterogeneity in populations involved. we performed a systematic search of multiple bibliographic databases, up to october 2013, to identify all studies on detection of mmtv-lv dna in human breast cancer using polymerase chain reaction (pcr) and conducted the first comprehensive meta-an ...201424936218
the e2f transcription factors regulate tumor development and metastasis in a mouse model of metastatic breast cancer.while the e2f transcription factors (e2fs) have a clearly defined role in cell cycle control, recent work has uncovered new functions. using genomic signature methods, we predicted a role for the activator e2f transcription factors in the mouse mammary tumor virus (mmtv)-polyomavirus middle t oncoprotein (pymt) mouse model of metastatic breast cancer. to genetically test the hypothesis that the e2fs function to regulate tumor development and metastasis, we interbred mmtv-pymt mice with e2f1, e2f ...201424934442
the wnt signaling antagonist dickkopf-1 directs lineage commitment and promotes survival of the preimplantation embryo.successful embryonic development is dependent on factors secreted by the reproductive tract. dickkopf-1 (dkk1), an antagonist of the wingless-related mouse mammary tumor virus (wnt) signaling pathway, is one endometrial secretory protein potentially involved in maternal-embryo communication. the purpose of this study was to investigate the roles of dkk1 in embryo cell fate decisions and competence to establish pregnancy. using in vitro-produced bovine embryos, we demonstrate that exposure of emb ...201424858280
activation of noncanonical wnt signaling through wnt5a in visceral adipose tissue of obese subjects is related to inflammation.wingless-type mouse mammary tumor virus integration site family (wnt)-5a is a glycoprotein involved in the regulation of the inflammatory response by activating the noncanonical wnt signaling pathway. secreted frizzled-related protein (sfrp)-5 acts as a decoy receptor that binds and sequesters wnt5a, preventing activation of frizzled receptors and attenuating the noncanonical wnt signaling.201424840810
detection and identification of mouse mammary tumor virus-like dna sequences in blood and breast tissues of breast cancer patients.mouse mammary tumor virus (mmtv) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. the hypothesis that a retrovirus homologous to mmtv is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. therefore, the detection of mmtv-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. to detect the prevalence of mmtv in pak ...201424839004
maternal metabolic perturbations elicited by high-fat diet promote wnt-1-induced mammary tumor risk in adult female offspring via long-term effects on mammary and systemic phenotypes.many adult chronic diseases are thought to be influenced during early life by maternal nutrition; however, the underlying mechanisms remain largely unknown. obesity-related diseases may be due partly to high fat consumption. herein, we evaluated mammary tumor risk in female mouse mammary tumor virus-wnt-1 transgenic (tg) offspring exposed to high-fat diet (hfd) or control diet (cd) (45% and 17% kcal from fat, respectively) during gestation and lactation, with cd provided to progeny at weaning. i ...201424832086
conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype.mammary epithelial (me) cells cultured under conventional conditions senesce after several passages. here, we demonstrate that mouse me cells isolated from normal mammary glands or from mouse mammary tumor virus (mmtv)-neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (crcs) on irradiated fibroblasts in the presence of the rho kinase inhibitor y-27632. cell surface progenitor-associated markers are rapidly induced in normal mouse me-crcs relative to me ...201424831228
mammary cancer chemoprevention by withaferin a is accompanied by in vivo suppression of self-renewal of cancer stem cells.current dogma favors elimination of therapy-resistant cancer stem cells for chemoprevention of breast cancer. we showed recently that mammary cancer development in a transgenic mouse model (mouse mammary tumor virus-neu; mmtv-neu) was inhibited significantly upon treatment with withaferin a (wa), a steroidal lactone derived from a medicinal plant. herein, we demonstrate that the mammary cancer prevention by wa is accompanied by in vivo suppression of breast cancer stem cells (bcsc). in vitro mam ...201424824039
ew-7197, a novel alk-5 kinase inhibitor, potently inhibits breast to lung metastasis.advanced tumors produce an excessive amount of transforming growth factor β (tgfβ), which promotes tumor progression at late stages of malignancy. the purpose of this study was to develop anti-tgfβ therapeutics for cancer. we synthesized a novel small-molecule tgfβ receptor i kinase (activin receptor-like kinase 5) inhibitor termed n-[[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]methyl]-2-fluoroaniline (ew-7197), and we investigated its potential antimetastat ...201424817629
secreted phosphoprotein 1 is a determinant of lung function development in mice.secreted phosphoprotein 1 (spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting c3h/hej and jf1/msf mouse strains that have extremely divergent lung function. jf1/msf mice with diminished lung function had reduced lung spp1 transcript and protein during the peak stage of alveologenesis (postnatal day [p]14-p28) as compared with c3h/hej mice. in addition to a previously identified genetic variant that altered runt-related tran ...201424816281
protein kinase c beta in the tumor microenvironment promotes mammary tumorigenesis.protein kinase c beta (pkcβ) expression in breast cancer is associated with a more aggressive tumor phenotype, yet the mechanism for how pkcβ is pro-tumorigenic in this disease is still unclear. interestingly, while it is known that pkcβ mediates angiogenesis, immunity, fibroblast function and adipogenesis, all components of the mammary tumor microenvironment (tme), no study to date has investigated whether stromal pkcβ is functionally relevant in breast cancer. herein, we evaluate mouse mammary ...201424795864
overexpression of notch-regulated ankyrin repeat protein is associated with breast cancer cell proliferation.notch-regulated ankyrin repeat protein (nrarp) has been implicated in crosstalk between notch and wingless-type mouse mammary tumor virus integration site (wnt) signals during development. our study aimed to clarify its role in breast cancer cells.201424778018
mechanistic elucidation of the antitumor properties of withaferin a in breast cancer.withaferin a (wfa) is a steroidal lactone with antitumor effects manifested at multiple levels that are mechanistically obscure. using a phospho-kinase screening array, we discovered that wfa activated phosphorylation of the s6 kinase rsk (ribosomal s6 kinase) in breast cancer cells. pursuing this observation, we defined activation of extracellular signal-regulated kinase (erk)-rsk and ets-like transcription factor 1 (elk1)-chop (c-ebp homologous protein) kinase pathways in upregulating transcri ...201424732433
chromatin landscapes of retroviral and transposon integration profiles.the ability of retroviruses and transposons to insert their genetic material into host dna makes them widely used tools in molecular biology, cancer research and gene therapy. however, these systems have biases that may strongly affect research outcomes. to address this issue, we generated very large datasets consisting of ~ 120,000 to ~ 180,000 unselected integrations in the mouse genome for the sleeping beauty (sb) and piggybac (pb) transposons, and the mouse mammary tumor virus (mmtv). we ana ...201424721906
receptor revision in cd4 t cells is influenced by follicular helper t cell formation and germinal-center interactions.peripheral cd4 t cells in vβ5 transgenic (tg) c57bl/6j mice undergo tolerance to an endogenous superantigen encoded by mouse mammary tumor virus 8 (mtv-8) by either deletion or t-cell receptor (tcr) revision. revision is a process by which surface expression of the vβ5(+) tcr is down-regulated in response to mtv-8 and recombination activating genes are expressed to drive rearrangement of the endogenous tcrβ locus, effecting cell rescue through the expression of a newly generated, non-self-reacti ...201424706795
visualization of angiogenesis during cancer development in the polyoma middle t breast cancer model: molecular imaging with (r)-[11c]paq.vascular endothelial growth factor receptor 2 (vegfr2) is a crucial mediator of tumour angiogenesis. high expression levels of the receptor have been correlated to poor prognosis in cancer patients. reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. the aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the vegfr2-targeting positron emission tomography (p ...201424670127
effects of fibroblast growth factor 9 on steroidogenesis and control of fgfr2iiic mrna in porcine granulosa cells.the objectives of this study were to investigate the effects of fibroblast growth factor 9 (fgf9) on hormone-stimulated porcine granulosa cell proliferation and steroid production and to further elucidate the hormonal and developmental control of fgfr2iiic gene expression in granulosa cells. porcine ovaries were collected from a local slaughterhouse and granulosa cells were collected from small to medium (1 to 5 mm) follicles for 5 in vitro studies that were conducted. cells were cultured for 48 ...201424664559
mislocalization of the cell polarity protein scribble promotes mammary tumorigenesis and is associated with basal breast cancer.scribble (scrib) localizes to cell-cell junctions and regulates establishment of epithelial cell polarity. loss of expression of scrib functions as a tumor suppressor in drosophila and mammals; conversely, overexpression of scrib promotes epithelial differentiation in mammals. here, we report that scrib is frequently amplified, mrna overexpressed, and protein is mislocalized from cell-cell junctions in human breast cancers. high levels of scrib mrna are associated with poor clinical prognosis, i ...201424662921
overexpression of erbb4 jm-a cyt-1 and cyt-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis.human epidermal growth factor receptor (erbb4/her4) belongs to the epidermal growth factor receptor/erbb family of receptor tyrosine kinases. while erbb1, erbb2 and erbb3 are often overexpressed or activated in breast cancer, and are oncogenic, the role of erbb4 in breast cancer is uncertain. some studies suggest a tumor suppressor role of erbb4, while other reports suggest an oncogenic potential. alternative splicing of erbb4 yields four major protein products, these spliced isoforms differ in ...201425516216
prevalence of hmtv in breast carcinomas and unaffected tissue from mexican women.breast cancer is a complex multifactorial genetic disease. among other factors, race and, to an even greater extent, viruses are known to influence the development of this heterogeneous disease. it has been reported that mmtv-like (hmtv) gene sequences with a 90 to 98% homology to mouse mammary tumor virus are found in several populations with a prevalence range of 0 to 74%. in the mexican population, 4.2% of patients with breast cancer exhibit the presence of hmtv (mmtv-like) sequences. the aim ...201425495285
oncogenic effects of wnt5a in epstein-barr virus‑associated nasopharyngeal carcinoma.the molecular events that drive the progression of epstein-barr virus (ebv)-associated nasopharyngeal carcinoma (npc) are still to be elucidated. here, we report for the first time the pathogenic significance of an npc-associated gene, wingless-type mmtv integration site family, member 5a (wnt5a) and the contribution of ebv to its expression. wnt5a is a representative wnt protein that activates non-canonical wnt signalling. with regard to its role in carcinogenesis, there is conflicting evidence ...201424626628
mouse mammary tumor virus-based vector transduces non-dividing cells, enters the nucleus via a tnpo3-independent pathway and integrates in a less biased fashion than other retroviruses.mouse mammary tumor virus (mmtv) is a complex, milk-born betaretrovirus, which preferentially infects dendritic cells (dc) in the gastrointestinal tract and then spreads to t and b lymphocytes and finally to the mammary gland. it is not clear how the prototypic betaretrovirus infects mucosal dcs and naïve lymphocytes as these cells are considered to be non-proliferative. studies of mmtv biology have been hampered by the difficulty of obtaining sufficient virus/vector titers after transfection of ...201424779422
hepatic interferon-stimulated genes are differentially regulated in the liver of chronic hepatitis c patients with different interleukin-28b genotypes.pretreatment up-regulation of hepatic interferon (ifn)-stimulated genes (isgs) has a stronger association with the treatment-resistant interleukin (il)28b minor genotype (mi; tg/gg at rs8099917) than with the treatment-sensitive il28b major genotype (ma; tt at rs8099917). we compared the expression of isgs in the liver and blood of 146 patients with chronic hepatitis c who received pegylated ifn and ribavirin combination therapy. gene expression profiles in the liver and blood of 85 patients wer ...201424311440
one-step separation of myristoylated and nonmyristoylated retroviral matrix proteins.n-terminal myristoylation of retroviral matrix proteins is essential for the targeting of the gag polyproteins to the plasma membrane. to investigate the effect of the myristoylation on the structure and membrane binding ability of the matrix proteins, it is necessary to prepare their myristoylated forms. we present purification of myristoylated matrix proteins of the mouse mammary tumor virus and murine leukemia virus, two morphogenetically distinct retroviruses. the proteins were expressed in ...201324056256
glucocorticoid-mediated period2 induction delays the phase of circadian rhythm.glucocorticoid (gc) signaling synchronizes the circadian rhythm of individual peripheral cells and induces the expression of circadian genes, including period1 (per1) and period2 (per2). however, no gc response element (gre) has been reported in the per2 promoter region. here we report the molecular mechanisms of per2 induction by gc signaling and its relevance to the regulation of circadian timing. we found that gc prominently induced per2 expression and delayed the circadian phase. the overlap ...201323620290
metabolic alterations in mammary cancer prevention by withaferin a in a clinically relevant mouse model.efficacy of withaferin a (wa), an ayurvedic medicine constituent, for prevention of mammary cancer and its associated mechanisms were investigated using mouse mammary tumor virus-neu (mmtv-neu) transgenic model.201323821767
revisiting a role for a mammary tumor retrovirus in human breast cancer.there remains great controversy as to whether mouse mammary tumor virus (mmtv), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. on one hand, retroviruses such as human t-cell lymphotropic virus and human immunodeficiency virus (hiv) are known causative agents of cancer (in the case of hiv, albeit, indirectly), but attempts to associate other retroviruses with human cancers have been difficult. a r ...201323580334
apobec3 inhibition of mouse mammary tumor virus infection: the role of cytidine deamination versus inhibition of reverse transcription.the apolipoprotein b editing complex 3 (apobec3) family of proteins is a group of intrinsic antiviral factors active against a number of retroviral pathogens, including hiv in humans and mouse mammary tumor virus (mmtv) in mice. apobec3 restricts its viral targets through cytidine deamination of viral dna during reverse transcription or via deaminase-independent means. here, we used virions from the mammary tissue of mmtv-infected inbred wild-type mice with different allelic apobec3 variants (ap ...201323449789
no association between epstein-barr virus and mouse mammary tumor virus with breast cancer in mexican women.breast cancer is the most frequent malignancy affecting women worldwide. it has been suggested that infection by epstein barr virus (ebv), mouse mammary tumor virus or a similar virus, mmtv-like virus (mmtv-lv), play a role in the etiology of the disease. however, studies looking at the presence of these viruses in breast cancer have produced conflicting results, and this possible association remains controversial. here, we used polymerase chain reaction assay to screen specific sequences of ebv ...201324131889
carcinogenic viruses and solid cancers without sufficient evidence of causal association.viral infections are important risk factors for tumor development in humans. selected types of cancers, either lymphomas or carcinomas, for which there is sufficient evidence in humans of a causal association with specific viruses, have been identified. experimental and clinical data on the possible association of other tumor types and carcinogenic viruses are presently controversial. in this article, we review the current evidence on the relationship between breast, colorectal and lung cancers ...201323280523
is there a role for cyclophilin inhibitors in the management of primary biliary cirrhosis?autoimmune hepatitis (aih) and primary biliary cirrhosis (pbc) are poorly understood autoimmune liver diseases. immunosuppression is used to treat aih and ursodeoxycholic acid is used to slow the progression of pbc. nevertheless, a proportion of patients with both disorders progress to liver failure. following liver transplantation, up to a third of patients with pbc experience recurrent disease. moreover a syndrome referred to as "de novo aih" occurs in a proportion of patients regardless of ma ...201323348060
comparison of prostate-specific promoters and the use of psp-driven virotherapy for prostate cancer.prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in men today. although virus-based gene therapy is a promising strategy to combat advanced prostate cancer, its current effectiveness is limited partially due to inefficient cellular transduction in vivo. to overcome this obstacle, conditional oncolytic viruses (such as conditional replication adenovirus (crad)) are developed to specifically target prostate without (or with minimal) systemic tox ...201323484134
csf1r inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by cd8(+) t cells.increased numbers of tumor-infiltrating macrophages correlate with poor disease outcome in patients affected by several types of cancer, including breast and prostate carcinomas. the colony stimulating factor 1 receptor (csf1r) signaling pathway drives the recruitment of tumor-associated macrophages (tams) to the neoplastic microenvironment and promotes the differentiation of tams toward a pro-tumorigenic phenotype. twelve clinical trials are currently evaluating agents that target the csf1/csf1 ...201324498562
endogenous mouse mammary tumor viruses (mtv): new roles for an old virus in cancer, infection, and immunity.mouse mammary tumor viruses are beta-retroviruses that exist in both exogenous (mmtv) and endogenous (mtv) forms. exogenous mmtv is transmitted via the milk of lactating animals and is capable of inducing mammary gland tumors later in life. mmtv has provided a number of critical models for studying both viral infection as well as human breast cancer. in addition to the horizontally transmitted mmtv, most inbred mouse strains contain permanently integrated mtv proviruses within their genome that ...201324324930
epidemiological and phylogenetic analysis of institutional mouse parvoviruses.mouse parvoviruses (mpvs) are small, single-stranded, 5 kb dna viruses that are subclinical and endemic in many laboratory mouse colonies. mpvs cause more distinctive deleterious effects in immune-compromised or genetically-engineered mice than immuno-competent mice. at the university of louisville (u of l), there was an unexpected increase of mpv sero-positivity for mpv infections in mouse colonies between january 2006 and february 2007, resulting in strategic husbandry changes aimed at control ...201323545399
virions at the gates: receptors and the host-virus arms race.all viruses need to bind to specific receptor molecules on the surface of target cells to initiate infection. virus-receptor binding is highly specific, and this specificity determines both the species and the cell type that can be infected by a given virus. in some well-studied cases, the virus-binding region on the receptor has been found to be unrelated to the receptor's normal cellular function. resistance to virus infection can thus evolve by selection of mutations that alter amino acids in ...201323723739
bisected, complex n-glycans and galectins in mouse mammary tumor progression and human breast cancer.bisected, complex n-glycans on glycoproteins are generated by the glycosyltransferase mgat3 and cause reduced cell surface binding of galectins. previously, we showed that mgat3 reduces growth factor signaling and retards mammary tumor progression driven by the polyoma middle t antigen (pymt) expressed in mammary epithelium under the mouse mammary tumor virus (mmtv) promoter. however, the penetrance of the tumor phenotype became variable in mixed fvb/n and c57bl/6 female mice and we therefore in ...201324037315
wnt11 expression in rat dental pulp and promotional effects of wnt signaling on odontoblast differentiation.congenital anomalies of wingless-type mouse mammary tumor virus (mmtv) integration site family (wnt) are frequently accompanied with tooth and dentin abnormality. the aim of this study was to investigate the effects of wnt signaling on odontoblast differentiation of mouse dental papilla cells (mdps). mouse dental papilla cells were cultured in α-modified minimum essential medium containing 10% fetal bovine serum and antibiotics. odontoblast differentiation was induced by bone morphogenic protein ...201323998262
aldosterone stimulates fibronectin synthesis in renal fibroblasts through mineralocorticoid receptor-dependent and independent mechanisms.in addition to its role in regulation of salt transport in the kidney, the mineralocorticoid hormone aldosterone plays an independent role as a mediator of kidney injury and progression of chronic kidney disease. studies in both animal models and patients have shown that aldosterone enhances the accumulation of extracellular matrix and progression of fibrosis in the kidney. however, the cellular mechanisms that lead to aldosterone-dependent fibrogenesis are poorly understood. in this study we fi ...201323994292
mir-155-mediated loss of c/ebpβ shifts the tgf-β response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer.during breast cancer progression, transforming growth factor-beta (tgf-β) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (emt), invasion and metastasis. however, the mechanisms involved in this switch are not clear. we found that loss of ccaat-enhancer binding protein beta (c/ebpβ), a differentiation factor for the mammary epithelium, was associated with signs of emt in triple-negative human breast cancer, and in invasive areas of mamma ...201323955085
class i lysine deacetylases facilitate glucocorticoid-induced transcription.nuclear receptors use lysine acetyltransferases and lysine deacetylases (kdacs) in regulating transcription through histone acetylation. lysine acetyltransferases interact with steroid receptors upon binding of an agonist and are recruited to target genes. kdacs have been shown to interact with steroid receptors upon binding to an antagonist. we have shown previously that kdac inhibitors (kdacis) potently repress the mouse mammary tumor virus promoter through transcriptional mechanisms and impai ...201323946490
molecular mechanism of slc5a8 inactivation in breast cancer.slc5a8 is a putative tumor suppressor that is inactivated in more than 10 different types of cancer, but neither the oncogenic signaling responsible for slc5a8 inactivation nor the functional relevance of slc5a8 loss to tumor growth has been elucidated. here, we identify oncogenic hras (hras(g12v)) as a potent mediator of slc5a8 silencing in human nontransformed normal mammary epithelial cell lines and in mouse mammary tumors through dnmt1. further, we demonstrate that loss of slc5a8 increases c ...201323918800
human mammary tumor virus (hmtv) in endometrial carcinoma.human mammary tumor virus (hmtv) is 90% to 98% homologous to mouse mammary tumor virus, the etiological agent of mammary tumors in mice. human mammary tumor virus sequences were found in 40% of the breast cancers studied in both american and australian women. in addition, 10% of endometrial carcinomas studied in australian women also contained hmtv sequences. we have explored the possibility that endometrial cancer of american women may also contain hmtv.201323873177
late developing mammary tumors and hyperplasia induced by a low-oncogenic variant of mouse mammary tumor virus (mmtv) express genes identical to those induced by canonical mmtv.the canonical milk-transmitted mouse mammary tumor virus (mmtv) of c3h mice (c3h-mmtv) rapidly induces tumors in 90% of infected animals by 8 months of age. pro-viral insertions of c3h-mmtv into genomic dna results in the overexpression of common core insertion site (cis) genes, including wnt1/10b, rspo2, and fgf3. conversely, infection by either the endogenous mtv-1 virus (in c3hf) or the exogenous nodule-inducing virus (niv) (in balb/c niv) induces premalignant mammary lesions and tumors with ...201323866257
the dietary terpene lupeol targets colorectal cancer cells with constitutively active wnt/β-catenin signaling.aberrant activation of the wingless-type mouse mammary tumor virus integration site family (wnt)/β-catenin signaling pathway is the most common modification, and often considered, a hallmark of colorectal cancer (crc). typically in this pathway the β-catenin translocates from the cytoplasm to the nucleus, where it functions as a transcription regulator of several genes that support tumor formation and progression. thus, any agent that could attenuate the translocation of β-catenin could be extre ...201323836602
genomic dna of mcf-7 breast cancer cells not an ideal choice as positive control for pcr amplification based detection of mouse mammary tumor virus-like sequences.the identification of the etiology of breast cancer is a crucial research issue for the development of an effective preventive and treatment strategies. researchers are exploring the possible involvement of mouse mammary tumor virus (mmtv) in causing human breast cancer. hence, it becomes very important to use a consistent positive control agent in pcr amplification based detection of mmtv-like sequence (mmtv-ls) in human breast cancer for accurate and reproducible results. this study was done t ...201323835033
expression of a phosphorylated substrate domain of p130cas promotes pymt-induced c-src-dependent murine breast cancer progression.elevated expression of p130cas (crk-associated substrate)/bcar1 (breast cancer antiestrogen resistance 1) in human breast tumors is a marker of poor prognosis and poor overall survival. p130cas is a downstream target of the tyrosine kinase c-src. signaling mediated by p130cas through its phosphorylated substrate domain (sd) and interaction with effector molecules directly promotes tumor progression. we previously developed a constitutively phosphorylated p130cas sd molecule, src*/sd (formerly re ...201323825155
bst-2/tetherin is overexpressed in mammary gland and tumor tissues in mmtv-induced mammary cancer.bst-2 restricts mmtv replication, but once infection has established, mmtv modulates bst-2 levels. mmtv-directed bst-2 modulation is tissue-specific and dependent on infection and neoplastic transformation status of cells. in the lymphoid compartment of infected mice, bst-2 expression is first upregulated and then significantly downregulated regardless of absence or presence of mammary tumors. however, in mammary gland tissues, upregulation of bst-2 expression is dependent on the presence of mam ...201323806386
lack of detection of the mouse mammary tumor-like virus (mmtv) env gene in iranian women breast cancer using real time pcr.mouse mammary tumor virus (mmtv) is the major cause of mammary tumors in mice. there is limited controversial evidence about the probable etiologic role of mmtv- like virus in human breast cancer.201323803058
response to fish specific reproductive hormones and endocrine disrupting chemicals of a sertoli cell line expressing endogenous receptors from an endemic cyprinid gnathopogon caerulescens.fish sertoli cells play a critical role in spermatogenesis by mediating androgen and progestogen signaling. their hormonal response, however, considerably differ among species. therefore it would be ideal to use sertoli cells originated from the fish of interest to investigate the effects of hormones as well as endocrine disrupting chemicals (edcs). the aim of this study was to investigate the responses to reproductive hormones and edcs of a sertoli cell line that we established from an endemic ...201323770217
analysis of tumor heterogeneity and cancer gene networks using deep sequencing of mmtv-induced mouse mammary tumors.cancer develops through a multistep process in which normal cells progress to malignant tumors via the evolution of their genomes as a result of the acquisition of mutations in cancer driver genes. the number, identity and mode of action of cancer driver genes, and how they contribute to tumor evolution is largely unknown. this study deployed the mouse mammary tumor virus (mmtv) as an insertional mutagen to find both the driver genes and the networks in which they function. using deep insertion ...201323690930
dietary chemopreventative benzyl isothiocyanate inhibits breast cancer stem cells in vitro and in vivo.a small subset of mammary tumor-initiating cells (also known as breast cancer stem cells; bcsc), characterized by expression of different markers [cd44(high)/cd24(low)/epithelial-specific antigen (esa)+], aldehyde dehydrogenase-1 (aldh1) activity, and ability to form mammospheres under ultra-low attachment culture conditions, are suspected to evade conventional therapies leading to disease recurrence. elimination of both therapy-sensitive epithelial tumor cells and therapy-resistant bcsc is ther ...201323661606
repression of adipogenesis through promotion of wnt/β-catenin signaling by tis7 up-regulated in adipocytes under hypoxia.although tetradecanoyl phorbol acetate induced sequence-7 (tis7) has been identified as a co-activator/repressor of gene transcription in different eukaryotic cells, little attention has been paid to the functionality of tis7 in adipocytes. here, we evaluated the possible role of tis7 in mechanisms underlying the regulation of adipogenesis. tis7 expression was preferentially up-regulated in white adipose tissues (wat) of obesity model mice as well as in pre-adipocytic 3t3-l1 cells cultured under ...201323517917
role for compartmentalization in nephron progenitor differentiation.embryonic nephron progenitor cells are segregated in molecularly distinct compartments of unknown function. our study reveals an integral role for bone morphogenetic protein-smad in promoting transition of progenitors from the primitive cbp/p300-interacting transactivator 1 expressing (cited1+) compartment to the uniquely sine oculis-related homeobox 2 expressing (six2-only) compartment where they become inducible by wingless-type mouse mammary tumor virus integration site family member (wnt)/β- ...201323487745
biochemical characterization of novel retroviral integrase proteins.integrase is an essential retroviral enzyme, catalyzing the stable integration of reverse transcribed dna into cellular dna. several aspects of the integration mechanism, including the length of host dna sequence duplication flanking the integrated provirus, which can be from 4 to 6 bp, and the nucleotide preferences at the site of integration, are thought to cluster among the different retroviral genera. to date only the spumavirus prototype foamy virus integrase has provided diffractable cryst ...201324124581
lack of evidence for human t-lymphotropic virus type 1 and mouse mammary tumor-like virus involvement in the genesis of childhood acute lymphoblastic leukemia.in mexico city, the incidence of childhood acute lymphoblastic leukemia (all) is one of the highest in the world; epidemiologic evidence suggests that infectious agents could be involved in the genesis of this disease. early transmitted oncogenic retroviruses infecting lymphocytes are important candidates.201324019395
protein tyrosine kinase 6 regulates mammary gland tumorigenesis in mouse models.protein tyrosine kinase 6 (ptk6, also called brk) is an intracellular tyrosine kinase expressed in the majority of human breast tumors and breast cancer cell lines, but its expression has not been reported in normal mammary gland. to study functions of ptk6 in vivo, we generated and characterized several transgenic mouse lines with expression of human ptk6 under control of the mouse mammary tumor virus (mmtv) long terminal repeat. ectopic active ptk6 was detected in luminal epithelial cells of m ...201324323291
uncovering novel actors in astrocyte-neuron crosstalk in parkinson's disease: the wnt/β-catenin signaling cascade as the common final pathway for neuroprotection and self-repair.parkinson's disease (pd) is a common neurodegenerative disorder characterized by progressive loss of dopaminergic (daergic) neuronal cell bodies in the substantia nigra pars compacta and gliosis. the cause and mechanisms underlying the demise of nigrostriatal daergic neurons are ill-defined, but interactions between genes and environmental factors are recognized to play a critical role in modulating the vulnerability to pd. current evidence points to reactive glia as a pivotal factor in pd patho ...201323461676
chemoprevention activity of dipyridamole in the mmtv-pymt transgenic mouse model of breast cancer.dipyridamole (dpm) is widely used to prevent strokes and vascular thrombosis. combination therapy of dpm and antimetabolites has shown synergistic anticancer activity. this study investigated the chemopreventive effects of dpm in the mouse mammary tumor virus promoter-driven polyoma middle t oncoprotein metastatic breast cancer model. we also investigated the effects of dpm on gene and mirna expression. chemopreventive activity was assessed by comparing the time to onset of palpable lesions, pri ...201323447563
a novel point mutation in the dna-binding domain (dbd) of the human glucocorticoid receptor causes primary generalized glucocorticoid resistance by disrupting the hydrophobic structure of its dbd.primary generalized glucocorticoid resistance is a rare genetic condition characterized by partial end-organ insensitivity to glucocorticoids. most affected subjects present with clinical manifestations of mineralocorticoid and androgen excess. the condition has been associated with inactivating mutations in the human glucocorticoid receptor (hgr) gene, which impair the molecular mechanisms of hgrα action, thereby reducing tissue sensitivity to glucocorticoids.201323426617
in vitro assessment of the inflammatory breast cancer cell line sum 149: discovery of 2 single nucleotide polymorphisms in the rnase l gene.inflammatory breast cancer (ibc) is a rare, highly aggressive form of breast cancer. the mechanism of ibc carcinogenesis remains unknown. we sought to evaluate potential genetic risk factors for ibc and whether or not the ibc cell lines sum149 and sum190 demonstrated evidence of viral infection.201323386909
hormone-sensing cells require wip1 for paracrine stimulation in normal and premalignant mammary epithelium.the molecular circuitry of different cell types dictates their normal function as well as their response to oncogene activation. for instance, mice lacking the wip1 phosphatase (also known as ppm1d; protein phosphatase magnesium-dependent 1d) have a delay in her2/neu (human epidermal growth factor 2), but not wnt1-induced mammary tumor formation. this suggests a cell type-specific reliance on wip1 for tumorigenesis, because alveolar progenitor cells are the likely target for transformation in th ...201323369183
characterization of rare mammary tumours appearing on the neck of riii/sa mice infected with mouse mammary tumour virus.riii/sa and c3h mice harbour milk-borne mouse mammary tumour virus (mmtv) and develop mammary tumours at a high incidence. these mammary tumours usually arise ventrally and/or on the sides of the animals. in the present study, some mice of both strains were observed to have tumours in the dorsal neck area. histological analysis of the tumours indicated their similarity to mammary tumours induced by mmtv oncogenesis. the neck tumours were found by thin-section electron microscopy to contain both ...201323351506
redirection of human cancer cells upon the interaction with the regenerating mouse mammary gland microenvironment.tumorigenesis is often described as a result of accumulated mutations that lead to growth advantage and clonal expansion of mutated cells. there is evidence in the literature that cancer cells are influenced by the microenvironment. our previous studies demonstrated that the mouse mammary gland is capable of redirecting mouse cells of non-mammary origins as well as mouse mammary tumor virus (mmtv)-neu transformed cells toward normal mammary epithelial cell fate during gland regeneration. interes ...201324709643
how glucocorticoid receptors modulate the activity of other transcription factors: a scope beyond tethering.the activity of the glucocorticoid receptor (gr), a nuclear receptor transcription factor belonging to subclass 3c of the steroid/thyroid hormone receptor superfamily, is typically triggered by glucocorticoid hormones. apart from driving gene transcription via binding onto glucocorticoid response elements in regulatory regions of particular target genes, gr can also inhibit gene expression via transrepression, a mechanism largely based on protein:protein interactions. hereby gr can influence the ...201323267834
flotillin-2 deficiency leads to reduced lung metastases in a mouse breast cancer model.flotillin microdomains, specialized lipid raft domains in cell membranes, serve as physical platforms for many different molecules important in crucial intracellular signaling pathways. flotillin-2 (flot2), together with flotillin-1, is a marker for lipid raft microdomains distinct from caveolar lipid rafts, and has been implicated in the progression of cancer and metastasis formation. based largely on studies in xenograft models, flotillin-2 has been implicated in the progression of multiple ty ...201323146906
nucleolar trafficking of the mouse mammary tumor virus gag protein induced by interaction with ribosomal protein l9.the mouse mammary tumor virus (mmtv) gag protein directs the assembly in the cytoplasm of immature viral capsids, which subsequently bud from the plasma membranes of infected cells. mmtv gag localizes to discrete cytoplasmic foci in mouse mammary epithelial cells, consistent with the formation of cytosolic capsids. unexpectedly, we also observed an accumulation of gag in the nucleoli of infected cells derived from mammary gland tumors. to detect gag-interacting proteins that might influence its ...201323135726
the distribution, clearance, and safety of an anti-mmp-9 dnazyme in normal and mmtv-pymt transgenic mice.catalytic oligonucleotides, known as dnazymes, are a new class of nucleic acid-based gene therapy that have recently been used in preclinical animal studies to treat various cancers. in this study the systemic distribution, pharmacokinetics, and safety of intravenously administered anti-mmp (matrix metalloproteinase)-9 dnazyme (am9d) were determined in healthy fvb and in mmtv-polyoma virus middle t (pymt) transgenic mice bearing mammary tumors. mmp-9 is known to be involved in tumor cell develop ...201324083396
dmp1α inhibits her2/neu-induced mammary tumorigenesis.our recent study shows a pivotal role of dmp1 in quenching hyperproliferative signals from her2 to the arf-p53 pathway as a safety mechanism to prevent breast carcinogenesis. to directly demonstrate the role of dmp1 in preventing her2/neu-driven oncogenic transformation, we established flag-dmp1α transgenic mice (mdtg) under the control of the mouse mammary tumor virus (mmtv) promoter. the mice were viable but exhibited poorly developed mammary glands with markedly reduced milk production; thus ...201324205004
sirt1 catalytic activity has little effect on tumor formation and metastases in a mouse model of breast cancer.the protein deacetylase sirt1 has been implicated in the regulation of a large number of cellular processes that are thought to be required for cancer initiation and progression. there are conflicting data that make it unclear whether sirt1 functions as an oncogene or tumor suppressor. to assess the effect of sirt1 on the emergence and progression of mammary tumors, we crossed mice that harbor a point mutation that abolishes sirt1 catalytic activity with mice carrying the polyoma middle t transg ...201324278473
mammary cells with active wnt signaling resist erbb2-induced tumorigenesis.aberrant activation of wnt signaling is frequent in human malignancies. in normal epithelial tissues, including the breast, wnt signaling is active only in a subset of cells, but it is unknown whether this subset of wnt signaling-active cells is at increased risk of carcinogenesis. we created transgenic mice (top-tva) in which the synthetic wnt-responsive promoter top controlled the gene encoding tva, which confers susceptibility to infection by the retroviral vector rcas. thus, only cells in wh ...201324265712
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