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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
heterogeneity in erk activity as visualized by in vivo fret imaging of mammary tumor cells developed in mmtv-neu mice.human epidermal growth factor receptor2/neu, which is overexpressed in about 30% of human breast cancers, transduces growth signals in large part via the ras-raf-mek-erk pathway. nevertheless, it is a matter of controversy whether high erk activity in breast cancer tissues correlates with better or worse prognosis, leaving the role of erk activity in the progression of breast cancers unresolved. to address this issue, we live-imaged erk activity in mammary tumors developed in mouse mammary tumor ...201524632612
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
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
metformin selectively targets tumor-initiating cells in erbb2-overexpressing breast cancer models.metformin is an oral biguanide used for type ii diabetes. epidemiologic studies suggest a link between metformin use and reduced risk of breast and other types of cancers. erbb2-expressing breast cancer is a subgroup of tumors with poor prognosis. previous studies demonstrated that metformin is a potent inhibitor of erbb2-overexpressing breast cancer cells; metformin treatment extends the life span and impedes mammary tumor development in erbb2 transgenic mice in vivo. however, the mechanisms of ...201424322659
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
wnt/β-catenin signaling regulates follicular development by modulating the expression of foxo3a signaling components.wnt signaling is an evolutionarily conserved pathway that regulates cell proliferation, differentiation and apoptosis. to investigate the possible role of wnt signaling in the regulation of ovarian follicular development, secondary follicles were isolated and cultured in vitro in the presence or absence of its activator (licl or wnt3a) or inhibitor (iwr-1). we have demonstrated that activation of β-catenin signals by activators dramatically suppressed follicular development by increasing granulo ...201424246780
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
mtorc1/2 targeted by n-3 polyunsaturated fatty acids in the prevention of mammary tumorigenesis and tumor progression.although epidemiological and preclinical studies have shown the preventative effects of n-3 polyunsaturated fatty acids (pufas) on breast cancer, inconsistencies still remain in the data and the underlying mechanisms remain unclear. in this study, we identified mammalian target of rapamycin (mtor) signaling, which plays an essential role in cell proliferation and breast tumorigenesis, as a target of n-3 pufas. in breast cancer cell lines, n-3 pufas rapidly and efficiently suppress both mtor comp ...201424096482
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
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
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
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
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
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
genes affected by mouse mammary tumor virus (mmtv) proviral insertions in mouse mammary tumors are deregulated or mutated in primary human mammary tumors.the accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. we have used a mouse model in which the carcinogen is the mouse mammary tumor virus (mmtv) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. identification of the genes and signaling pathways affected in mmtv-induced mouse mammary lesions provides a rationale for determining whether ge ...201223131872
promoter-context as a determinant of glucocorticoid receptor-responsiveness to activation of p38 and jnk mitogen-activated protein (map) kinases.map kinases jnk and p38 play an important role in many immune and inflammatory processes, whereas glucocorticoids exert immunosuppressive and anti-inflammatory activities. we found previously that activation of p38 or jnk inhibits glucocorticoid receptor (gr)-mediated transcriptional activation of a mouse mammary tumor virus (mmtv) promoter-driven luciferase construct in hela cells. it appears that this effect is dna regulatory element-specific, since p38 or jnk activation stimulates gr-dependen ...201223047944
canid progesterone receptors lack activation function 3 domain-dependent activity.progesterone regulates multiple behavioral, physiological, and pathological aspects of female reproductive biology through its two progesterone receptors (prs), pr-b and the truncated pr-a. pr-b is necessary for mammary gland development in mice and, compared with pr-a, is overall a stronger transactivator of target genes due to an additional activation function 3 (af3) domain. in dogs, known for their high sensitivity to progesterone-induced mammary cancer, the pr-b function was studied. canine ...201223041671
mammary tumor development is directly inhibited by lifelong n-3 polyunsaturated fatty acids.despite the advocacy that diet may be a significant contributor to cancer prevention, there is a lack of direct evidence from epidemiological and experimental studies to substantiate such claims. experimental studies suggest that n-3 polyunsaturated fatty acids (n-3 pufa) from marine oils may reduce breast cancer risk, however, findings are equivocal. thus, in this study, novel transgenic mouse models were employed to provide, for the first time, direct evidence for an anti-cancer role of n-3 pu ...201323026490
mouse mammary tumor virus suppresses apoptosis of mammary epithelial cells through itam-mediated signaling.many receptors in hematopoietic cells use a common signaling pathway that relies on a highly conserved immunoreceptor tyrosine-based activation motif (itam), which signals through src family tyrosine kinases. itam-bearing proteins are also found in many oncogenic viruses, including the mouse mammary tumor virus (mmtv) envelope (env). we previously showed that mmtv env expression transformed normal mammary epithelial cells and that src kinases were important mediators in this transformation. to s ...201223015704
epigenetic regulation of cell adhesion and communication by enhancer of zeste homolog 2 in human endothelial cells.the histone methyltransferase enhancer of zeste homolog 2 (ezh2) mediates trimethylation of lysine 27 in histone 3, which acts as a repressive epigenetic mark. ezh2 is essential for maintaining pluripotency of stem cells, but information on its role in differentiated cells is sparse. whole-genome mrna expression arrays identified 964 genes that were regulated by >2-fold 72 hours after small interfering rna-mediated silencing of ezh2 in human umbilical vein endothelial cells. among them, genes as ...201222966008
generation of a novel mmtv-tta transgenic mouse strain for the targeted expression of genes in the embryonic and postnatal mammary gland.we have generated a new and improved transgenic mouse strain that permits a temporally controlled expression of transgenes throughout mammary gland development. high expression of the tetracycline-regulatible transactivator (tta) under control of the mouse mammary tumor virus long terminal repeat (mmtv-ltr) is restricted to mammary epithelial cells and the salivary gland. the novel mmtv-tta mouse strain induces a sustained transactivation of responder transgenes, which can be swiftly suppressed ...201222952764
remodeling of endogenous mammary epithelium by breast cancer stem cells.poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (csc) participate in remodeling is unknown. we performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. first, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. to assess csc-specific remodeling events, we isolated csc from mmtv-wnt1 (mouse mammary tumor virus long-term ...201222899386
biomarkers of phenethyl isothiocyanate-mediated mammary cancer chemoprevention in a clinically relevant mouse model.phenethyl isothiocyanate (peitc) is a natural plant compound with chemopreventative potential against some cancers and the ability to induce apoptosis in breast cancer cells.201222859850
manganese superoxide dismutase is dispensable for post-natal development and lactation in the murine mammary gland.mammary gland development is a multistage process requiring tightly regulated spatial and temporal signalling pathways. many of these pathways have been shown to be sensitive to oxidative stress. understanding that the loss of manganese superoxide dismutase (sod2) leads to increased cellular oxidative stress, and that the loss or silencing of this enzyme has been implicated in numerous pathologies including those of the mammary gland, we sought to examine the role of sod2 in mammary gland develo ...201222834911
adenovirus-mediated wnt10b overexpression induces hair follicle regeneration.hair follicles periodically undergo regeneration. the balance between activators and inhibitors may determine the time required for telogen hair follicles to reenter anagen. we previously reported that wnt10b (wingless-type mouse mammary tumor virus integration site family member 10b) could promote the growth of hair follicles in vitro. to unveil the roles of wnt10b in hair follicle regeneration, we established an in vivo mouse model using intradermal injection. on the basis of this model, we fo ...201322832493
targeting the ikkβ/mtor/vegf signaling pathway as a potential therapeutic strategy for obesity-related breast cancer.clinical correlation studies have clearly shown that obesity is associated with breast cancer risk and patient survival. although several potential mechanisms linking obesity and cancers have been proposed, the detailed molecular mechanism of obesity-mediated breast tumorigenesis has not yet been critically evaluated. in this study, we evaluated the effects of obesity on mammary tumor initiation and progression using mice with genetic and diet-induced obesity bearing mammary tumor xenografts and ...201222826466
the gain of function of p53 cancer mutant in promoting mammary tumorigenesis.tumor suppressor p53 is critical for suppressing all types of human cancers, including breast cancer. the p53 gene is somatically mutated in over half of all human cancers. the majority of the p53 mutations are missense mutations, leading to the expression of the full-length p53 mutants. several hotspot mutations, including r175h, are frequently detected in human breast cancer. p53 cancer mutants not only lose tumor suppression activity but, more problematically, also gain new oncogenic activiti ...201322824795
effects of fibroblast growth factor 9 (fgf9) on steroidogenesis and gene expression and control of fgf9 mrna in bovine granulosa cells.gene expression of fibroblast growth factor-9 (fgf9) is decreased in granulosa cells (gc) of cystic follicles compared with normal dominant follicles in cattle. the objectives of this study were to investigate the effects of fgf9 on gc steroidogenesis, gene expression, and cell proliferation and to determine the hormonal control of gc fgf9 production. gc were collected from small (1-5 mm) and large (8-22 mm) bovine follicles and treated in vitro with various hormones in serum-free medium for 24 ...201222798350
the signal peptide of mouse mammary tumor virus-env: a phosphoprotein tumor modulator.mouse mammary tumor virus (mmtv) is associated primarily with mammary carcinomas and lymphomas. the signal peptide of the mmtv envelope precursor is uniquely targeted to nucleoli of cells that harbor the virus, where it can function as a nuclear export factor for intron-containing transcripts. antibodies to this signal peptide, which we refer to as p14, were previously shown to label nucleoli in a subset of human breast cancers. to look for additional cellular functions of p14, different mutants ...201222740636
no effect of ngal/lipocalin-2 on aggressiveness of cancer in the mmtv-pymt/fvb/n mouse model for breast cancer.ngal/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. it is suggested to confer a proliferative advantage to cancer cells. its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer models. this was recently confirmed in two mouse models of spontaneous breast cancer in wild-type and lipocalin-2-deficient mice. we used a similar strategy using a different mouse strain. lipocalin-2-defic ...201222737251
follicle-stimulating hormone regulation of estradiol production: possible involvement of wnt2 and β-catenin in bovine granulosa cells.follicle-stimulating hormone regulation of estrogen biosynthesis in the adult rodent ovary requires β-catenin (ctnnb1), but whether ctnnb1 is involved in fsh-induced estrogen production in cattle is unknown. to elucidate the effect of fsh in regulating specific wingless-type mouse mammary tumor virus integration site (wnt)/ctnnb1 pathway components in bovine folliculogenesis and steroidogenesis, granulosa cells and follicular fluid were collected from large antral follicles (8 to 22 mm) from ova ...201222696613
leptin regulates cyclin d1 in luminal epithelial cells of mouse mmtv-wnt-1 mammary tumors.leptin, an adipose secreted cytokine, is implicated in mammary cancer stem cell self-renewal and tumor growth in murine mammary tumor virus (mmtv)-wnt-1 transgenic mice. in vitro studies indicate that leptin induces expression of cyclin d1, a cell-cycle control protein necessary for mammary tumor development. the aim of the present study was to assess cyclin d1 expression in spontaneous tumors that develop in the mmtv-wnt-1 transgenic mice and interrogate the in vivo effect of leptin.201222692856
phytosterols inhibit the tumor growth and lipoprotein oxidizability induced by a high-fat diet in mice with inherited breast cancer.dietary phytosterol supplements are readily available to consumers since they effectively reduce plasma low-density lipoprotein cholesterol. several studies on cell cultures and xenograft mouse models suggest that dietary phytosterols may also exert protective effects against common cancers. we examined the effects of a dietary phytosterol supplement on tumor onset and progression using the well-characterized mouse mammary tumor virus polyoma virus middle t antigen transgenic mouse model of inhe ...201322658647
overexpression of follistatin in the mouse epididymis disrupts fluid resorption and sperm transit in testicular excurrent ducts.activin is a well-established modulator of male and female reproduction that stimulates the synthesis and secretion of follicle-stimulating hormone. nonpituitary effects of activin have also been reported, although the paracrine actions of this growth factor in several reproductive tissues are not well understood. to identify the paracrine functions of activin during mammary gland morphogenesis and tumor progression, we produced transgenic mice that overexpress follistatin (fst), an intrinsic in ...201222649074
impaired mouse mammary gland growth and development is mediated by melatonin and its mt1g protein-coupled receptor via repression of erα, akt1, and stat5.to determine whether melatonin, via its mt(1)  g protein-coupled receptor, impacts mouse mammary gland development, we generated a mouse mammary tumor virus (mmtv)-mt1-flag-mammary gland over-expressing (mt1-moe) transgenic mouse. increased expression of the mt(1) -flag transgene was observed in the mammary glands of pubescent mt1-moe transgenic female mice, with further significant increases during pregnancy and lactation. mammary gland whole mounts from mt1-moe mice showed significant reductio ...201222582905
different levels of testicular organization during gonadal differentiation in b6.y(tir) mice manifesting sex reversal.b6.y(tir) (mice with y chromosome from a strain in tirano, italy, and autosomes and x-chromosomes from the b6 strain) mice provide an excellent model for analysing sex development that occurs during gonadal differentiation; however, the molecular mechanisms that contribute to sex reversal are unclear. our aim has been to establish which molecular events participate in this sex reversal. the pattern of gene expression related to testicular [sry (sex-determining region of the y chromosome), sox9 ( ...201222582735
mmtv-neu mice deficient in stat1 are susceptible to develop ovarian teratomas.signal transducer and activator of transcription 1 (stat1) serves in the protection of the organism against pathogens and other harmful insults. it is implicated in innate immune response, immunosurveillance, tumor-suppression, and the response to genotoxic as well as oxidative stress. we report here that 9 of 140 examined stat1 deficient mouse mammary tumor virus-neu (mmtv-neu) mice developed differentiated ovarian teratomas, which histologically resemble benign dermatoid cysts. conventional ka ...201222562203
early vascular deficits are correlated with delayed mammary tumorigenesis in the mmtv-pymt transgenic mouse following genetic ablation of the ng2 proteoglycan.the neuron-glial antigen 2 (ng2) proteoglycan promotes pericyte recruitment and mediates pericyte interaction with endothelial cells. in the absence of ng2, blood vessel development is negatively impacted in several pathological models. our goal in this study was to determine the effect of ng2 ablation on the early development and function of blood vessels in mammary tumors in the mammary tumor virus-driven polyoma middle t (mmtv-pymt) transgenic mouse, and to correlate these vascular changes wi ...201222531600
suppression of frizzled-2-mediated wnt/ca²⁺ signaling significantly attenuates intracellular calcium accumulation in vitro and in a rat model of traumatic brain injury.traumatic brain injury (tbi) can dramatically increase levels of intracellular calcium (ca²⁺). the association between wnt5a/frizzled-2 (wingless-type mouse mammary tumor virus integration site family member 5a/fzd2) signaling and ca²⁺ cellular homeostasis in lower vertebrates has been well documented. however, little is known about wnt5a/fzd2 signaling in mammalian nerve cells, or whether ca²⁺ accumulation after tbi is mediated through this pathway. we hypothesized that an activated wnt5a/fzd2 ...201222521824
conditional deletion of β-catenin in mammary epithelial cells of ron receptor, mst1r, overexpressing mice alters mammary tumorigenesis.the ron receptor tyrosine kinase (macrophage stimulating 1 receptor) is overexpressed in approximately 50% of human breast cancers. transgenic mice overexpressing ron in the mammary epithelium [mouse mammary tumor virus driven (mmtv)-ron expressing mice] develop mammary tumors that exhibit up-regulation of β-catenin and β-catenin target genes. β-catenin has been shown to be a mediator of mammary tumorigenesis in various breast cancer models, including downstream of ron. however, the in vivo impa ...201222474186
selenoproteins reduce susceptibility to dmba-induced mammary carcinogenesis.selenium is an essential micronutrient in the diet of humans and other mammals. based largely on animal studies and epidemiological evidence, selenium is purported to be a promising cancer chemopreventive agent. however, the biological mechanisms by which chemopreventive activity takes place are poorly understood. it remains unclear whether selenium acts in its elemental form, through incorporation into organic compounds, through selenoproteins or any combination of these. the purpose of this st ...201222436612
8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists.the progesterone receptor (pr) plays a key role in reproduction and is important in cancers of the reproductive tract. current pr antagonists usually compete for progestin binding in the pr ligand-binding pocket and often exhibit cross-binding with other members of the steroid receptor family. using stably transfected cells expressing reporter genes, a set of ∼150 theophylline analogues were screened for their ability to inhibit progesterone, estrogen, glucocorticoid and androgen signaling. the ...201222421057
notch signaling and breast cancer.it has been more than two decades since notch has been identified as an oncogene in mouse mammary tumor virus-infected mice. since this discovery, activated notch signaling and up-regulation of tumor-promoting notch target genes have been observed in human breast cancer. in addition, high expression of notch ligands and receptors has been shown to correlate with poor outcome in this malignancy. notch affects multiple cellular processes including stem cell maintenance, cell fate specification, di ...201222399352
focal adhesion kinase contributes to proliferative potential of erbb2 mammary tumour cells but is dispensable for erbb2 mammary tumour induction in vivo.activation of focal adhesion kinase (fak) is hypothesized to play an important role in the pathogenesis of human breast cancer.201222373082
multiple cystic sweat gland tumors in transgenic mice.here we describe gross and microscopic sweat gland tumors found in a transgenic mouse model of breast cancer, which had transforming growth factor α under the control of mouse mammary tumor virus promoter (mmtv-tgfα). initially, 20% of the mice in the colony were affected. cystic lesions formed on the phalanges, palmar surfaces of the metacarpals, and plantar surfaces of the metatarsals. the lesions were multifocal and nonulcerated with straw-colored fluid, ranging in size from 1 to 30 mm at the ...201222330648
contribution of cxcl12 secretion to invasion of breast cancer cells.neu (her2/erbb2) is overexpressed in 25% to 30% of human breast cancer, correlating with a poor prognosis. researchers in previous studies who used the mouse mammary tumor virus neu-transgenic mouse model (mmtv-neu) demonstrated that the neu-yb line had increased production of cxcl12 and increased metastasis, whereas the neu-yd line had decreased metastasis. in this study, we examined the role of increased production of cxcl12 in tumor cell invasion and malignancy.201222314082
hypoxia-inducible factor 1α promotes primary tumor growth and tumor-initiating cell activity in breast cancer.overexpression of the oxygen-responsive transcription factor hypoxia-inducible factor 1α (hif-1α) correlates with poor prognosis in breast cancer patients. the mouse mammary tumor virus polyoma virus middle t (mmtv-pymt) mouse is a widely utilized preclinical mouse model that resembles human luminal breast cancer and is highly metastatic. prior studies in which the pymt model was used demonstrated that hif-1α is essential to promoting carcinoma onset and lung metastasis, although no differences ...201222225988
3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1- methylpyridine oxalate, a novel xanomeline derivative, improves neural cells proliferation and survival in adult mice.the present study analyzed the influence of 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1-methylpyridine oxalate (euk1001), a novel xanomeline derivative of the m1/m4 receptor agonist, on hippocampal neurogenesis in adult c57bl6 mice. results showed that 15-day euk1001 treatment via intraperitoneal injection promoted neural cell proliferation in the dentate gyrus, although cell differentiation did not change. the majority of bromodeoxyuridine-positive ce ...201225806054
prevalence of ebv, hpv and mmtv in pakistani breast cancer patients: a possible etiological role of viruses in breast cancer.breast cancer being a multifactorial disease, the role of infectious agent in development of disease is of great interest. the high incidence of breast cancer around the world has woken the interest in a viral etiology of breast cancer. despite decades of research, no etiologic factor(s) for human breast cancer has been known and the quest for a contributing cause has all but been abandoned during the past years. recent investigations have linked breast cancer to viral infections, such as epstei ...201728705719
the role of β-catenin in the initiation and metastasis of ta2 mice spontaneous breast cancer.purpose: tientsin albino 2 (ta2) mice have a high incidence of spontaneous breast cancer. tumor initiation is related to mouse mammary tumor virus (mmtv) infection. mmtv is hormonally regulated and may promote tumor formation via wnt/β-catenin signaling pathway. this study attempts to clarify the relationship between β-catenin expression and the initiation and metastasis of spontaneous breast cancer in ta2 mice. materials and methods: pathological samples illustrating the development of spontane ...201728819413
trail, wnt, sonic hedgehog, tgfβ, and mirna signalings are potential targets for oral cancer therapy.clinical studies and cancer cell models emphasize the importance of targeting therapies for oral cancer. the tumor necrosis factor-related apoptosis-inducing ligand (trail) is highly expressed in cancer, and is a selective killing ligand for oral cancer. signaling proteins in the wingless-type mouse mammary tumor virus (mmtv) integration site family (wnt), sonic hedgehog (shh), and transforming growth factor β (tgfβ) pathways may regulate cell proliferation, migration, and apoptosis. accordingly ...201728708091
exome sequencing reveals a novel homozygous splice site variant in the wnt1 gene underlying osteogenesis imperfecta type 3.backgroundosteogenesis imperfecta (oi) is a heritable bone fragility disorder usually caused by dominant variants in col1a1 or col1a2 genes. over the last few years, 17 genes including 12 autosomal recessive and five autosomal dominant forms of oi, involved in various aspects of bone formation, have been identified.methodswhole-exome sequencing followed by conventional sanger sequencing was performed in a single affected individual (iv-3) in a family.resultshere, we report the clinical and genet ...201728665926
the wnt/β-catenin signalling pathway inhibitor sclerostin is a biomarker for early atherosclerosis in obesity.sclerostin is an inhibitor of the wingless-type mouse mammary tumor virus integration site family/β-catenin signalling pathway (wβcsp), which plays an important role in bone metabolism and in vascular biology. it could act protective regarding atherosclerosis development through its effect on wβcsp in vascular cells. nevertheless, results of studies analyzing association between circulating sclerostin level (csl) and atherosclerotic diseases (ad) are showing conflicting results. the aim of study ...201728625128
the drosophila orthologue of the int6 onco-protein regulates mitotic microtubule growth and kinetochore structure.int6/eif3e is a highly conserved component of the translation initiation complex that interacts with both the 26s proteasome and the cop9 signalosome, two complexes implicated in ubiquitin-mediated protein degradation. the int6 gene was originally identified as the insertion site of the mouse mammary tumor virus (mmtv), and later shown to be involved in human tumorigenesis. here we show that depletion of the drosophila orthologue of int6 (int6) results in short mitotic spindles and deformed cent ...201728505193
molecular signaling of progesterone, growth hormone, wnt, and her in mammary glands of dogs, rodents, and humans: new treatment target identification.mammary tumors are the most common form of neoplasia in the bitch. female dogs are protected when they are spayed before the first estrus cycle, but this effect readily disappears and is already absent when dogs are spayed after the second heat. as the ovaries are removed during spaying, ovarian steroids are assumed to play an essential role in tumor development. the sensitivity toward tumor development is already present during early life, which may be caused by early mutations in stem cells du ...201728451590
low prevalence of human mammary tumor virus (hmtv) in breast cancer patients from myanmar.human mammary tumor virus (hmtv) is 90-95% homologous to mouse mammary tumor virus (mmtv), one of the causal agents of murine mammary tumors. hmtv (mmtv-like) sequences were reported to be present in human breast cancers from several populations with a prevalence range of 0-78%; however, the prevalence of hmtv in breast cancers from myanmar remains unknown.201728413435
characterization of an integrated, endogenous mouse mammary tumor virus-like (mmtv) betaretrovirus genome in a black syrian hamster (mesocricetus auratus).retroviruses (family retroviridae) are important agents of humans and animals. this study reports the detection and complete genome characterization of a novel endogenous retrovirus from the black syrian hamster (mesocricetus auratus) with a squamous cell skin tumor. the proviral genome, tentatively named black syrian hamster retrovirus (bshrv/2013/hun, mk304634), was 8784 nucleotide in length with typical full-length betaretrovirus genome organization of 5'ltr-gag-pro-pol-env-3'ltr and with a c ...201931404669
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