| cyclin d1 kinase activity is required for the self-renewal of mammary stem and progenitor cells that are targets of mmtv-erbb2 tumorigenesis. | transplantation studies have demonstrated the existence of mammary progenitor cells with the ability to self-renew and regenerate a functional mammary gland. although these progenitors are the likely targets for oncogenic transformation, correlating progenitor populations with certain oncogenic stimuli has been difficult. cyclin d1 is required for lobuloalveolar development during pregnancy and lactation as well as mmtv-erbb2- but not mmtv-wnt1-mediated tumorigenesis. using a kinase-deficient cy ... | 2010 | 20129248 |
| disruption of the lcn2 gene in mice suppresses primary mammary tumor formation but does not decrease lung metastasis. | based largely on studies in xenograft models, lipocalin-2 (lcn2) has been implicated in the progression of multiple types of human tumors, including breast cancer. here we examine the role of lcn2 in mammary tumorigenesis and lung metastasis using an in vivo molecular genetics approach. we crossed a well-characterized transgenic mouse model of breast cancer, the mmtv-pymt (mouse mammary tumor virus-polyoma middle t antigen) mouse, with two independent gene-targeted lcn2(-/-) mouse strains of the ... | 2010 | 20133630 |
| metabolomic changes accompanying transformation and acquisition of metastatic potential in a syngeneic mouse mammary tumor model. | breast cancer is the most common cancer type for women in the western world. despite decades of research, the molecular processes associated with breast cancer progression are still inadequately defined. here, we focus on the systematic alteration of metabolism by using the state of the art metabolomic profiling techniques to investigate the changes of 157 metabolites during the progression of normal mouse mammary epithelial cells to an isogenic series of mammary tumor cell lines with increasing ... | 2010 | 20139083 |
| conditional overexpression of tgf-beta1 disrupts mouse salivary gland development and function. | transforming growth factor-beta (tgf-beta) signaling is known to affect salivary gland physiology by influencing branching morphogenesis, regulating ecm deposition, and controlling immune homeostasis. to study the role of tgf-beta1 in the salivary gland, we created a transgenic mouse (beta1(glo)) that conditionally overexpresses active tgf-beta1 upon genomic recombination by cre recombinase. beta1(glo) mice were bred with an mmtv (mouse mammary tumor virus)-cre (mc) transgenic line that expresse ... | 2010 | 20142803 |
| orphan receptor kinase ror2 is expressed in the mouse uterus. | wingless-type mouse mammary tumor virus integration site family, member 5a (wnt5a), is expressed in mouse decidua and is thought to play an important role in decidualization. we examined expression of the receptor for wnt5a, receptor tyrosine kinase-like orphan receptor 2 (ror2), in the uteri of cycling and pregnant mice. | 2010 | 20149452 |
| the bhlh/pas transcription factor singleminded 2s promotes mammary gland lactogenic differentiation. | we have previously demonstrated that the bhlh/pas transcription factor, singleminded 2s (sim2s), is required for proper mammary ductal morphogenesis and luminal epithelial differentiation. furthermore, loss of sim2s in breast cancer cells resulted in downregulation of epithelial markers and acquisition of a basal-like phenotype. the objective of this study was to further define the role of sim2s in mammary differentiation. we found that sim2s is developmentally regulated throughout mammary gland ... | 2010 | 20150276 |
| constitutively active stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of cten. | the transcription factor signal transducer and activator of transcription 3 (stat3) is constitutively activated in tumors of different origin, but the molecular bases for stat3 requirement are only partly understood. to evaluate the contribution of enhanced stat3 activation in a controlled model system, we generated knock-in mice wherein a mutant constitutively active stat3c allele replaces the endogenous wild-type allele. stat3c could enhance the tumorigenic power of the rat neu oncogene in mou ... | 2010 | 20215508 |
| does plasminogen activator inhibitor-1 drive lymphangiogenesis? | the purpose of this study is to explore the function of plasminogen activator inhibitor-1 (pai-1) during pathological lymphangiogenesis. pai-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. protease system's role in lymphangiogenesis is unknown yet. thus, based on its important pro-angiogenic effect, we hypothesized that pai-1 may regu ... | 2010 | 20300183 |
| integrin-linked kinase has a critical role in erbb2 mammary tumor progression: implications for human breast cancer. | elevated expression of the integrin-linked kinase (ilk) has been observed in a variety of cancers and has been further correlated with poor clinical outcome. here, we show that mammary epithelial disruption of ilk results in a profound block in mammary tumor induction. consistent with these observations, inhibition of ilk function in erbb2-expressing cells with small molecule inhibitor or rna interference resulted in profound block in their in vitro invasive properties due to the induction of ap ... | 2010 | 20305688 |
| mouse mammary tumor virus-like sequences in human breast cancer. | mouse mammary tumor virus (mmtv) sequences have been reported to be present in some human breast cancers, but it is unclear whether they have any causal role. in mice, mmtv promotes tumor formation indirectly by insertional mutagenesis of wnt oncogenes that lead to their activation. in this study, we investigated the status of wnt-1 in human breast cancers harboring mmtv-like sequences encoding viral envelope (env) genes. we confirmed the detection of env sequences in the nucleus of human breast ... | 2010 | 20388779 |
| the bisecting glcnac on n-glycans inhibits growth factor signaling and retards mammary tumor progression. | the branching of complex n-glycans attached to growth factor receptors promotes tumor progression by prolonging growth factor signaling. the addition of the bisecting glcnac to complex n-glycans by mgat3 has varying effects on cell adhesion, cell migration, and hepatoma formation. here, we show that chinese hamster ovary cells expressing mgat3 and the polyoma middle t (pymt) antigen have reduced cell proliferation and growth factor signaling dependent on a galectin lattice. the mgat3 gene is not ... | 2010 | 20395209 |
| time course of paclitaxel-induced apoptosis in an experimental model of virus-induced breast cancer. | early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin v. (99m)tc-labeled annexin v has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. t ... | 2010 | 20395330 |
| mmtv promoter-regulated caveolin-1 overexpression yields defective parenchymal epithelia in multiple exocrine organs of transgenic mice. | caveolin-1 (cav-1) is a major structural protein of caveolae, specialized plasma membrane invaginations that are involved in a cell-specific fashion in diverse cell activities such as molecular transport, cell adhesion, and signal transduction. in normal adult mammals, cav-1 expression is abundant in mesenchyme-derived cells but relatively low in epithelial parenchyma. however, epithelial cav-1 overexpression is associated with development and/or progression of many carcinomas. in this study, we ... | 2010 | 20399205 |
| dna of mouse mammary tumor virus-like virus is present in human tumors influenced by hormones. | mouse mammary tumor virus (mmtv) is a hormonally regulated, oncogenic virus of mice. mmtv-like virus dna has previously been detected in human breast cancers, liver disease, and liver cancers. it is hypothesized that local hormonal effects might be of primary importance in determining mmtv-like virus detection in human tumors. mmtv-like virus envelope (env) dna was determined using nested pcr in 89 ovarian, 147 prostate, 50 endometrial, 141 skin, and 51 lung cancers. viral-positive sequences wer ... | 2010 | 20419820 |
| perk promotes cancer cell proliferation and tumor growth by limiting oxidative dna damage. | to proliferate and expand in an environment with limited nutrients, cancer cells co-opt cellular regulatory pathways that facilitate adaptation and thereby maintain tumor growth and survival potential. the endoplasmic reticulum (er) is uniquely positioned to sense nutrient deprivation stress and subsequently engage signaling pathways that promote adaptive strategies. as such, components of the er stress-signaling pathway represent potential antineoplastic targets. however, recent investigations ... | 2010 | 20453876 |
| mechanism of inhibition of mmtv-neu and mmtv-wnt1 induced mammary oncogenesis by raralpha agonist am580. | we hypothesized that specific activation of a single retinoic acid receptor-alpha (raralpha), without direct and concurrent activation of rarbeta and gamma, will inhibit mammary tumor oncogenesis in murine models relevant to human cancer. a total of 50 uniparous mouse mammary tumor virus (mmtv)-neu and 50 nuliparous mmtv-wnt1 transgenic mice were treated with raralpha agonist (retinobenzoic acid, am580) that was added to the diet for 40 (neu) and 35 weeks (wnt1), respectively. among the shared a ... | 2010 | 20453882 |
| transforming growth factor-beta regulator snon modulates mammary gland branching morphogenesis, postlactational involution, and mammary tumorigenesis. | snon is an important negative regulator of transforming growth factor-beta (tgf-beta) signaling that was originally identified as a transforming oncogene in chicken embryonic fibroblasts. both pro-oncogenic and antioncogenic activities of snon have been reported, but its function in normal epithelial cells has not been defined. in the mouse mammary gland, snon is expressed at relatively low levels, but it is transiently upregulated at late gestation before being downregulated during lactation an ... | 2010 | 20460516 |
| minireview: role of kinases and chromatin remodeling in progesterone signaling to chromatin. | steroid hormones regulate gene expression by interaction of their receptors with hormone-responsive elements on dna or with other transcription factors, but they can also activate cytoplasmic signaling cascades. rapid activation of erk by progestins via an interaction of the progesterone receptor (pr) with the estrogen receptor is critical for transcriptional activation of the mouse mammary tumor virus (mmtv) promoter and other progesterone target genes. erk activation leads to the phosphorylati ... | 2010 | 20484412 |
| cyclosporine a inhibits in vitro replication of betaretrovirus associated with primary biliary cirrhosis. | up to one-third of patients with primary biliary cirrhosis (pbc) experience recurrent disease following liver transplantation, which is associated with earlier and more severe recurrence in patients treated with tacrolimus as compared with cyclosporine a (csa). as the latter has known antiviral activity, we hypothesized that csa has the ability to inhibit the betaretrovirus characterized from patients with pbc. | 2010 | 20492501 |
| fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-wnt-1 mouse model of breast cancer. | fibroblast growth factor (fgf) cooperates with the wnt/beta-catenin pathway to promote mammary tumorigenesis. to investigate the mechanisms involved in fgf/wnt cooperation, we genetically engineered a model of inducible fgf receptor (ifgfr) signaling in the context of the well-established mouse mammary tumor virus-wnt-1 transgenic mouse. in the bigenic mice, ifgfr1 activation dramatically enhanced mammary tumorigenesis. expression microarray analysis did not show transcriptional enhancement of w ... | 2010 | 20501844 |
| loss of the heparan sulfate sulfotransferase, ndst1, in mammary epithelial cells selectively blocks lobuloalveolar development in mice. | considerable evidence indicates that heparan sulfate is essential for the development of tissues consisting of branching ducts and tubules. however, there are few examples where specific sulfate residues regulate a specific stage in the formation of such tissues. | 2010 | 20502530 |
| human mammary tumor virus in inflammatory breast cancer. | the authors have found that retroviral sequences with 85% to 95% homology to the mouse mammary tumor virus were present in 40% of the sporadic breast cancers of american women. these sequences were not found in normal breasts or other tumors. a whole proviral structure was detected in 2 tumors. breast cancer cells in culture were shown to contain and shed betaretroviral particles. this virus was designated human mammary tumor virus (hmtv). the authors have investigated the presence of hmtv seque ... | 2010 | 20503403 |
| no evidence of mmtv-like env sequences in specimens from the australian breast cancer family study. | numerous independent groups from a range of countries have reported a high prevalence of mouse mammary tumour virus (mmtv)-like env sequences in human breast cancer specimens, including a prevalence of almost 40% in australia. mmtv-like sag sequences and a completely integrated provirus have also been described. recently, it was reported that mmtv is capable of productive infection of human breast cells in vitro. conclusive demonstration of an association between mmtv and human breast cancer has ... | 2011 | 20512660 |
| adjusting transgene expression levels in lymphocytes with a set of inducible promoters. | inducible gene expression systems are powerful research tools and could be of clinical value in the future, with lymphocytes being likely prime application targets. however, currently available regulatable promoters exhibit variation in their efficiency in a cell line-dependent-manner and are notorious for basal leakiness or poor inducibility. data concerning the regulatory properties of different inducible promoters are scarce for lymphocytes. in the present study, we report a comprehensive ana ... | 2010 | 20527043 |
| cancer immunotherapy: focusing on the young, neglecting the old. | | 2010 | 20528222 |
| icm web: the interactive chromatin modeling web server. | the interactive chromatin modeling web server (icm web) is an interactive tool that allows users to rapidly assess nucleosome stability and fold sequences of dna into putative chromatin templates. icm web takes a sequence composed of as, cs, gs, and ts as input and generates (i) a nucleosome energy level diagram, (ii) coarse-grained representations of free dna and chromatin and (iii) plots of the helical parameters (tilt, roll, twist, shift, slide and rise) as a function of position. the user ca ... | 2010 | 20542915 |
| breast tumors: of mice and women. | for the past 20 years the mouse has served as a workhorse for studying the molecular underpinnings of human breast cancer. while some genetically engineered mouse mammary tumor models do not accurately recapitulate human disease (that is, the mmtv-neu model and her2-overexpressing human cancers), additional tumor models exist for studying the initiation, progression, and treatment of human breast cancer. the relationships between normal mouse mammary epithelial cells and tumor cells, however, ha ... | 2010 | 20550730 |
| notch1-induced mammary tumor development is cyclin d1-dependent and correlates with expansion of pre-malignant multipotent duct-limited progenitors. | members of the notch family are involved in the development of breast cancer in animal models and in humans. in young transgenic mice, expressing intracellular activated notch1 (n1(ic)) in mammary cells, we found that cd24(+) cd29(high) progenitor cells had enhanced survival, and were expanded through a cyclin d1-dependent pathway. this expansion positively correlated with the later cyclin d1-dependent formation of basal-like ductal tumors. this expanded population exhibited abnormal differentia ... | 2010 | 20562911 |
| limitations of a murine transgenic breast cancer model for studies of erythropoietin-induced tumor progression. | adverse effects of erythropoietin (epo) on tumor progression and survival were observed in recent phase 3 oncology trials. however, mechanisms remain poorly understood. we tested the effects of exogenous epo on murine b16f10 melanoma growth in a subcutaneous tumor transplant model, and for the first time, in a model of spontaneous tumor formation within autochthonous epithelial tissues using murine mammary tumor virus promoter polyoma virus middle t antigen (mmtv-pymt) transgenic mice. epo recep ... | 2010 | 20563259 |
| cooperative signaling between wnt1 and integrin-linked kinase induces accelerated breast tumor development. | breast cancer is genetically and clinically a heterogeneous disease. however, the exact contribution of different cell types and oncogenic mutations to this heterogeneity are not well understood. recently, we discovered an interaction between wnt and integrin-linked kinase (ilk) within the signaling cascade that regulates cell growth and survival. interestingly, mammary-specific expression of either one of these proteins has been shown to promote mammary tumorigenesis. in light of our recent fin ... | 2010 | 20565980 |
| retroviral rem protein requires processing by signal peptidase and retrotranslocation for nuclear function. | mouse mammary tumor virus (mmtv) is a complex murine retrovirus that encodes an hiv rev-like export protein, rem, from a doubly spliced version of envelope (env) mrna. previously, the n-terminal 98-amino acid sequence of rem, which is identical to env signal peptide (sp), and full-length rem were shown to be functional in a reporter assay that measures a postexport function. here we show that mmtv-infected cells or cells transfected with rem or env cdnas express sp, which is the active component ... | 2010 | 20566871 |
| linking human beta retrovirus infection with primary biliary cirrhosis. | several environmental agents have been linked with primary biliary cirrhosis (pbc) that include bacteria, xenobiotics and viruses. a human beta retrovirus (hbrv) related to mouse mammary tumor virus has been cloned and characterized from patients with pbc. this agent can be detected in the majority of patients' perihepatic lymph nodes by immunochemistry and rt-pcr. the hbrv has recently been isolated in culture and integration sites have been identified in the genome of patients to provide convi ... | 2010 | 20580176 |
| the embryonic transcription cofactor lbh is a direct target of the wnt signaling pathway in epithelial development and in aggressive basal subtype breast cancers. | limb-bud and heart (lbh) is a novel key transcriptional regulator of vertebrate development. however, the molecular mechanisms upstream of lbh and its role in adult development are unknown. here we show that in epithelial development, lbh expression is tightly controlled by wnt signaling. lbh is transcriptionally induced by the canonical wnt pathway, as evident by the presence of conserved functional t-cell factor (tcf)/lymphoid enhancer-binding factor (lef) binding sites in the lbh locus and ra ... | 2010 | 20606007 |
| beta-catenin (ctnnb1) promotes preovulatory follicular development but represses lh-mediated ovulation and luteinization. | wingless-type mouse mammary tumor virus integration site family (wnt)/beta-catenin (ctnnb1) pathway components are expressed in ovarian granulosa cells, direct female gonad development, and are regulated by the pituitary gonadotropins. however, the in vivo functions of ctnnb1 during preovulatory follicular development, ovulation, and luteinization remain unclear. using a mouse model ctnnb1((ex3)fl/fl);cyp19-cre (ctnnb1((ex3)gc-/-)), expressing dominant stable ctnnb1 in granulosa cells of small a ... | 2010 | 20610534 |
| adaptive evolution of mus apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate groove. | mouse apobec3 (ma3) is a cytidine deaminase with antiviral activity. ma3 is linked to the rfv3 virus resistance factor, a gene responsible for recovery from infection by friend murine leukemia virus, and ma3 allelic variants differ in their ability to restrict mouse mammary tumor virus. we sequenced ma3 genes from 38 inbred strains and wild mouse species, and compared the mouse sequence and predicted structure with human apobec3g (ha3g). an inserted sequence was identified in the virus restricti ... | 2010 | 20617165 |
| mouse mammary tumor-like virus and human breast cancer. | | 2010 | 20623182 |
| conditional knockout of fibronectin abrogates mouse mammary gland lobuloalveolar differentiation. | fibronectin (fn) plays an important part in the branching morphogenesis of salivary gland, lung, and kidney. here, we examine the effect of the conditional knockout of fn in the mammary epithelium [fn(mep-/-)] on postnatal mammary gland development, using cre-loxp-mediated gene knockout technology. our data show that fn deletion causes a moderate retardation in outgrowth and branching of the ductal tree in 5-week-old mice. these defects are partially compensated in virgin 16-week-old mice. howev ... | 2010 | 20624380 |
| base excision repair in a glucocorticoid response element: effect of glucocorticoid receptor binding. | dna repair takes place in the context of chromatin. previous studies showed that histones impair base excision repair (ber) of modified bases at both the excision and synthesis steps. we examined ber of uracil in a glucocorticoid response element (gre) complexed with the glucocorticoid receptor dna binding domain (gr-dbd). five substrates were designed, each containing a unique c-->u substitution within the mouse mammary tumor virus promoter, one located within each gre half-site and the others ... | 2010 | 20628060 |
| gu81, a vegfr2 antagonist peptoid, enhances the anti-tumor activity of doxorubicin in the murine mmtv-pymt transgenic model of breast cancer. | vascular endothelial growth factor (vegf) is a primary stimulant of angiogenesis under physiological and pathological conditions. anti-vegf therapy is a clinically proven strategy for the treatment of a variety of cancers including colon, breast, lung, and renal cell carcinoma. since vegfr2 is the dominant angiogenic signaling receptor, it has become an important target in the development of novel anti-angiogenic therapies. we have reported previously the development of an antagonistic vegfr2 pe ... | 2010 | 20673348 |
| increases in iga(+) b cells in peyer's patches during milk-borne mouse mammary tumor virus infection are influenced by toll-like receptor 4 and are completely dependent on the superantigen response. | mouse mammary tumor virus (mmtv) is a milk-borne betaretrovirus that has developed strategies to exploit and subvert the host immune system. although mammary glands are the final target of infection, peyer's patches (pp) are the entry site of the virus. herein, we show that the infection induces increases in the number of pp iga(+) b cells and higher expression of the α circular transcript, which is a specific marker of the switch to iga. in addition, iga(+) b-cell increases correlated with high ... | 2010 | 20685932 |
| beta1-integrin is dispensable for the induction of erbb2 mammary tumors but plays a critical role in the metastatic phase of tumor progression. | cross-talk between integrin receptors and activated growth factor receptors has been hypothesized to play a critical role in the initiation and progression of cancer. despite in vitro evidence documenting the important role of integrin receptors in the regulation of cancer cell proliferation, the relative contribution of the integrin receptors to the initiation and progression of tumors remains unclear. previous studies with a polyomavirus middle t mammary tumor model have indicated that targete ... | 2010 | 20713705 |
| inhibition of tumorigenesis driven by different wnt proteins requires blockade of distinct ligand-binding regions by lrp6 antibodies. | disregulated wnt/beta-catenin signaling has been linked to various human diseases, including cancers. inhibitors of oncogenic wnt signaling are likely to have a therapeutic effect in cancers. lrp5 and lrp6 are closely related membrane coreceptors for wnt proteins. using a phage-display library, we identified anti-lrp6 antibodies that either inhibit or enhance wnt signaling. two classes of lrp6 antagonistic antibodies were discovered: one class specifically inhibits wnt proteins represented by wn ... | 2010 | 20713706 |
| rapid extravasation and establishment of breast cancer micrometastases in the liver microenvironment. | to examine the interplay between tumor cells and the microenvironment during early breast cancer metastasis, we developed a technique for ex vivo imaging of murine tissue explants using two-photon microscopy. cancer cells in the liver and the lung were compared by imaging both organs at specific time points after the injection of the same polyomavirus middle t-initiated murine mammary tumor cell line. extravasation was greatly reduced in the lung compared with the liver, with 56% of tumor cells ... | 2010 | 20724460 |
| the noncanonical gag domains p8 and n are critical for assembly and release of mouse mammary tumor virus. | the mouse mammary tumor virus (mmtv) gag contains the unique domains pp21, p3, p8, and n. we investigated the contribution of these domains to particle assembly and found that the region spanning the p8 and n domains is critical for shape determination and assembly. deletion of pp21 and p3 reduced the number of released particles, but deletion of the n domain resulted in frequent formation of aberrant particles, while deletion of p8 severely impaired assembly. further investigation of p8 reveale ... | 2010 | 20739518 |
| mammalian target of rapamycin inhibition abrogates insulin-mediated mammary tumor progression in type 2 diabetes. | type 2 diabetes increases breast cancer risk and mortality, and hyperinsulinemia is a major mediator of this effect. the mammalian target of rapamycin (mtor) is activated by insulin and is a key regulator of mammary tumor progression. pharmacological mtor inhibition suppresses tumor growth in numerous mammary tumor models in the non-diabetic setting. however, the role of the mtor pathway in type 2 diabetes-induced tumor growth remains elusive. herein, we investigated whether the mtor pathway is ... | 2010 | 20801951 |
| pomegranate extract inhibits the proliferation and viability of mmtv-wnt-1 mouse mammary cancer stem cells in vitro. | pomegranate (punica granatum l.) is known to possess anticancer activities. the effects of a standardized extract of pomegranate (pe) on a mouse mammary cancer cell line (designated wa4) derived from mouse mmtv-wnt-1 mammary tumors were examined in this study. the wa4 cell line has been previously characterized as containing a majority of cells possessing stem cell characteristics. pe inhibited the proliferation of wa4 cells in a time- and concentration-dependent manner. this was due to an arres ... | 2010 | 20811693 |
| suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice. | glypican 3 (gpc3) belongs to a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. gpc3 is overexpressed in hepatocellular carcinoma. loss-of-function mutations of gpc3 result in simpson-golabi-behmel syndrome, an x-linked disorder characterized by overgrowth of multiple organs, including the liver. our previous study showed that gpc3 plays a negative regulatory role in hepatocyte proliferation, and this effect may involve cd81, a cell membrane tetraspani ... | 2010 | 20812357 |
| transgenic expression of human cathepsin b promotes progression and metastasis of polyoma-middle-t-induced breast cancer in mice. | elevated expression of the cysteine protease cathepsin b (ctsb) has been correlated with a poor prognosis for cancer patients. in order to model high ctsb expression in mammary cancer, transgenic mice expressing human ctsb were crossed with transgenic polyoma virus middle t oncogene breast cancer mice (mouse mammary tumor virus-pymt), resulting in a 20-fold increase in cathepsin b activity in the tumors of double-transgenic animals. ctsb expression did not affect tumor onset, but ctsb transgenic ... | 2011 | 20818432 |
| isoform-specific degradation of pr-b by e6-ap is critical for normal mammary gland development. | e6-associated protein (e6-ap), which was originally identified as an ubiquitin-protein ligase, also functions as a coactivator of estrogen (er-α) and progesterone (pr) receptors. to investigate the in vivo role of e6-ap in mammary gland development, we generated transgenic mouse lines that either overexpress wild-type (wt) human e6-ap (e6-ap(wt)) or ubiquitin-protein ligase-defective e6-ap (e6-ap(c833s)) in the mammary gland. here we show that overexpression of e6-ap(wt) results in impaired mamm ... | 2010 | 20829392 |
| a superantigen interacts with leishmanial infection in antigen-presenting cells to regulate cytokine commitment of responding cd4 t cells. | germ-line retroviral insertions in vertebrate genomes are implicated in the modulation of host immune responses. we demonstrate that cba/j mice, which carry the proviral integrants mammary tumor virus locus 6 (mtv6) and mammary tumor virus locus 7 (mtv7), are less resistant to infection with the protozoan pathogen leishmania major compared with closely related but mtv6-negative and mtv7-negative cba/caj mice. although both strains generated comparable l. major-specific cd4 t cell frequencies, t ... | 2010 | 20831385 |
| activation of murine double minute 2 by akt in mammary epithelium delays mammary involution and accelerates mammary tumorigenesis. | amplification or overexpression of murine double minute 2 (mdm2) promotes a variety of human tumors by degrading tumor suppressor proteins such as p53. phosphorylation of mdm2 on ser(166) and ser(186) by the survival kinase akt inhibits p53-mediated apoptosis. however, it is unclear whether this pathway contributes to normal or malignant pathophysiology in vivo. to address these questions, we generated transgenic mice expressing the akt-phosphorylated form of mdm2 (mdm2dds166d/s186d) in the mamm ... | 2010 | 20841468 |
| overexpression of the protein tyrosine phosphatase prl-2 correlates with breast tumor formation and progression. | the prl-1, prl-2, and prl-3 phosphatases are prenylated protein tyrosine phosphatases with oncogenic activity that are proposed to drive tumor metastasis. we found that prl-2 mrna is elevated in primary breast tumors relative to matched normal tissue, and also dramatically elevated in metastatic lymph nodes compared with primary tumors. prl-2 knockdown in metastatic mda-mb-231 breast cancer cells decreased anchorage-independent growth and cell migration, suggesting that the malignant phenotype o ... | 2010 | 20841483 |
| p190b rhogap has pro-tumorigenic functions during mmtv-neu mammary tumorigenesis and metastasis. | abstract: introduction: rho gtpases are overexpressed and hyperactivated in human breast cancers. deficiency of p190b rhogap, a major inhibitor of the rho gtpases, inhibits mouse mammary tumor virus long terminal repeat (mmtv)-neu/erbb2 mammary tumor formation and progression in part through effects within the stromal environment, suggesting that p190b function is pro-tumorigenic. to further investigate the potential pro-tumorigenic actions of p190b, we examined the effects of exogenous p190b ex ... | 2010 | 20860838 |
| maternal embryonic leucine zipper kinase is upregulated and required in mammary tumor-initiating cells in vivo. | maternal embryonic leucine zipper kinase (melk) is expressed in several developing tissues, in the adult germ line, and in adult neural progenitors. melk expression is elevated in aggressive undifferentiated tumors, correlating with poor patient outcome in human breast cancer. to investigate the role of melk in mammary tumorigenesis in vivo, we used a melk-green fluorescent protein (gfp) reporter mouse, which allows prospective isolation of melk-expressing cells based on gfp fluorescence. we fou ... | 2010 | 20861186 |
| presence of mmtv-like env gene sequences in human breast cancer. | | 2010 | 20872240 |
| mouse mammary tumor virus-like nucleotide sequences in canine and feline mammary tumors. | mouse mammary tumor virus (mmtv) has been speculated to be involved in human breast cancer. companion animals, dogs, and cats with intimate human contacts may contribute to the transmission of mmtv between mouse and human. the aim of this study was to detect mmtv-like nucleotide sequences in canine and feline mammary tumors by nested pcr. results showed that the presence of mmtv-like env and ltr sequences in canine malignant mammary tumors was 3.49% (3/86) and 18.60% (16/86), respectively. for f ... | 2010 | 20881168 |
| rank ligand mediates progestin-induced mammary epithelial proliferation and carcinogenesis. | rank ligand (rankl), a tnf-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor rank. mammary glands of rank- and rankl-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. it has been shown that rankl is responsible for the major proliferative response of mouse mammary epithelium to prog ... | 2010 | 20881963 |
| the normal mammary microenvironment suppresses the tumorigenic phenotype of mouse mammary tumor virus-neu-transformed mammary tumor cells. | the microenvironment of the mammary gland has been shown to exert a deterministic control over cells from different normal organs during murine mammary gland regeneration in transplantation studies. when mouse mammary tumor virus (mmtv)-neu-induced tumor cells were mixed with normal mammary epithelial cells (mecs) in a dilution series and inoculated into epithelium-free mammary fat pads, they were redirected to non-carcinogenic cell fates by interaction with untransformed mecs during regenerativ ... | 2010 | 20890308 |
| rarα1 control of mammary gland ductal morphogenesis and wnt1-tumorigenesis. | abstract: introduction: retinoic acid signaling pathways are disabled in human breast cancer suggesting a controlling role in normal mammary growth that might be lost in tumorigenesis. we tested a single receptor isotype, rarα1 (retinoic acid receptor isotype alpha, isoform 1), for its role in mouse mammary gland morphogenesis and mouse mammary tumor virus (mmtv)-wingless-related mmtv integration site 1 (wnt1)-induced oncogenesis. methods: the role of rarα1 in mammary morphogenesis was tested in ... | 2010 | 20923554 |
| mesenchymal stromal cells expressing erbb-2/neu elicit protective antibreast tumor immunity in vivo, which is paradoxically suppressed by ifn-gamma and tumor necrosis factor-alpha priming. | it is unknown whether mesenchymal stromal cells (msc) can regulate immune responses targeting tumor autoantigens of low immunogenicity. we tested here whether immunization with msc could break immune tolerance towards the erbb-2/her-2/neu tumor antigen and the effects of priming with ifn-γ and tumor necrosis factor-α (tnf-α) on this process. balb/c- and c57bl/6-derived msc were lentivirally transduced to express a kinase-inactive rat neu mutant (msc/neu). immunization of balb/c mice with nontrea ... | 2010 | 20924101 |
| enhanced genetic instability and dasatinib sensitivity in mammary tumor cells lacking nedd9. | elevated expression of the nedd9/hef1/cas-l scaffolding protein promotes tumor cell invasion and metastasis in multiple cancer cell types. conversely, generation of mammary tumors in the mouse mammary tumor virus (mmtv)-polyoma virus middle t (pyvt) genetic model is delayed by a nedd9(-/-) genotype. these activities arise from the role of nedd9 in assembling complexes and supporting activity of cancer signaling proteins, including fak, src, shc, and akt, and would support evaluation of nedd9 exp ... | 2010 | 20940402 |
| constitutive overexpression of id-1 in mammary glands of transgenic mice results in precocious and increased formation of terminal end buds, enhanced alveologenesis, delayed involution. | inhibitor of differentiation-1 (id-1) has been shown to play an essential role in cell proliferation, invasion, migration, and anti-apoptosis. however, the effect of id-1 in mammary gland development remains unknown. here, we generated mmtv-id-1 transgenic mice to study the role of id-1 in mammary gland development. in virgin mice, id-1 overexpression led to precocious development and delayed regression of terminal end buds (tebs) compared with wild-type mice. the number of brdu-positive cells a ... | 2011 | 20945346 |
| proteomic characterization of her2/neu-overexpressing breast cancer cells. | the receptor tyrosine kinase her2 is an oncogene amplified in invasive breast cancer and its overexpression in mammary epithelial cell lines is a strong determinant of a tumorigenic phenotype. accordingly, her2-overexpressing mammary tumors are commonly indicative of a poor prognosis in patients. several quantitative proteomic studies have employed two-dimensional gel electrophoresis in combination with ms/ms, which provides only limited information about the molecular mechanisms underlying her2 ... | 2010 | 20960451 |
| a compendium of the mouse mammary tumor biologist: from the initial observations in the house mouse to the development of genetically engineered mice. | for over a century, mouse mammary tumor biology and the associated mouse mammary tumor virus (mmtv) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology and neoplastic progression. however, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse mo ... | 2010 | 20961975 |
| vegfr-2 expression in tumor tissue of breast cancer patients. | | 2010 | 20963665 |
| upf1 senses 3'utr length to potentiate mrna decay. | the selective degradation of mrnas by the nonsense-mediated decay pathway is a quality control process with important consequences for human disease. from initial studies using rna hairpin-tagged mrnas for purification of messenger ribonucleoproteins assembled on transcripts with hiv-1 3' untranslated region (3'utr) sequences, we uncover a two-step mechanism for upf1-dependent degradation of mrnas with long 3'utrs. we demonstrate that upf1 associates with mrnas in a 3'utr length-dependent manner ... | 2010 | 21029861 |
| infection, stem cells and cancer signals. | the association of cancer with preceding parasitic infections has been observed for over 200 years. some such cancers arise from infection of tissue stem cells by viruses with insertion of viral oncogenes into the host dna (mouse polyoma virus, mouse mammary tumor virus). in other cases the virus does not insert its dna into the host cells, but rather commandeers the metabolism of the infected cells, so that the cells continue to proliferate and do not differentiate (human papilloma virus and ce ... | 2011 | 21044009 |
| heterogeneity of vascular and progenitor cell compartments in tumours from mmtv-pyvmt transgenic mice during mammary cancer progression. | transgenic mice are important tools for our study of breast cancer pathobiology. in order to evaluate changes in cell phenotype with breast cancer progression, we examined vascular and progenitor cell characteristics in tumours derived from mmtv-pyvmt mice. we performed dual-immunofluorescence staining for tie2, ptie2y1100, vegfr2 and pdgfr-β and the pan-endothelial marker pecam-1 (cd31) in 39 tumours from mmtv-pyvmt transgenic mice grouped by nuclear grade and tumour morphology. immunohistochem ... | 2010 | 21059124 |
| critical roles of dmp1 in human epidermal growth factor receptor 2/neu-arf-p53 signaling and breast cancer development. | human epidermal growth factor receptor 2 (her2) overexpression stimulates cell growth in p53-mutated cells while it inhibits cell proliferation in those with wild-type p53, but the molecular mechanism is unknown. the dmp1 promoter was activated by her2/neu through the phosphatidylinositol-3'-kinase-akt-nf-κb pathway, which in turn stimulated arf transcription. binding of p65 and p52 subunits of nf-κb was shown to the dmp1 promoter and that of dmp1 to the arf promoter on her2/neu overexpression. ... | 2010 | 21062982 |
| loss of stat1 from mouse mammary epithelium results in an increased neu-induced tumor burden. | type i and type ii classes of interferons (ifns) signal through the jak/stat1 pathway and are known to be important in adaptive and innate immune responses and in protection against tumors. although stat1 is widely considered a tumor suppressor, it remains unclear, however, if this function occurs in tumor cells (cell autonomous) or if stat1 acts primarily through immune cells. here, the question of whether stat1 has a cell autonomous role in mammary tumor formation was addressed in a mouse mode ... | 2010 | 21076615 |
| steroid receptor coactivator 1 deficiency increases mmtv-neu mediated tumor latency and differentiation specific gene expression, decreases metastasis, and inhibits response to ppar ligands. | the peroxisome proliferator activated receptor (ppar) subgroup of the nuclear hormone receptor superfamily is activated by a variety of natural and synthetic ligands. ppars can heterodimerize with retinoid x receptors, which have homology to other members of the nuclear receptor superfamily. ligand binding to ppar/rxrs results in recruitment of transcriptional coactivator proteins such as steroid receptor coactivator 1 (src-1) and creb binding protein (cbp). both src-1 and cbp are histone acetyl ... | 2010 | 21080969 |
| high-mannose glycans are elevated during breast cancer progression. | alteration in glycosylation has been observed in cancer. however, monitoring glycosylation changes during breast cancer progression is difficult in humans. in this study, we used a well-characterized transplantable breast tumor mouse model, the mouse mammary tumor virus-polyoma middle t antigen, to observe early changes in glycosylation. we have previously used the said mouse model to look at o-linked glycosylation changes with breast cancer. in this glycan biomarker discovery study, we examined ... | 2010 | 21097542 |
| mena deficiency delays tumor progression and decreases metastasis in polyoma middle-t transgenic mouse mammary tumors. | the actin binding protein mammalian enabled (mena), has been implicated in the metastatic progression of solid tumors in humans. mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. cells expressing high mena levels are part of the tumor microenvironment for metastasis (tmem), an anatomical structure that is predictive for risk of breast cancer metastasis. previously we have shown that forced expression of mena adenocarcino ... | 2010 | 21108830 |
| dynamic interaction of hdac1 with a glucocorticoid receptor-regulated gene is modulated by the activity state of the promoter. | although histone deacetylases (hdacs) are normally considered as co-repressors, hdac1 has been identified as a coactivator for the glucocorticoid receptor (gr) (qiu, y., zhao, y., becker, m., john, s., parekh, b. s., huang, s., hendarwanto, a., martinez, e. d., chen, y., lu, h., adkins, n. l., stavreva, d. a., wiench, m., georgel, p. t., schiltz, r. l., and hager, g. l. (2006) mol. cell 22, 669-679). furthermore, hdac1 is acetylated, and its acetylation level is linked to the transcription state ... | 2010 | 21127047 |
| the evidence does not support a viral etiology for primary biliary cirrhosis. | | 2010 | 21146570 |
| the evidence supports a viral aetiology for primary biliary cirrhosis. | | 2010 | 21147183 |
| apobec3 proteins expressed in mammary epithelial cells are packaged into retroviruses and can restrict transmission of milk-borne virions. | viruses, including retroviruses like human immunodeficiency virus (hiv) and mouse mammary tumor virus (mmtv), are transmitted from mother to infants through milk. lymphoid cells and antibodies are thought to provide mammary gland and milk-borne immunity. in contrast, little is known about the role of mammary epithelial cells (mecs). the apobec3 family of retroviral restriction factors is highly expressed in macrophages and lymphoid and dendritic cells. we now show that apobec3 proteins are also ... | 2010 | 21147467 |
| bcl-2-interacting mediator of cell death influences autoantigen-driven deletion and tcr revision. | peripheral cd4(+)vβ5(+) t cells are tolerized to an endogenous mouse mammary tumor virus superantigen either by deletion or tcr revision. through tcr revision, rag reexpression mediates extrathymic tcrβ rearrangement and results in a population of postrevision cd4(+)vβ5(-) t cells expressing revised tcrβ chains. we have hypothesized that cell death pathways regulate the selection of cells undergoing tcr revision to ensure the safety and utility of the postrevision population. in this study, we i ... | 2010 | 21148799 |
| tip30 deletion in mmtv-neu mice leads to enhanced egfr signaling and development of estrogen receptor-positive and progesterone receptor-negative mammary tumors. | estrogen receptor-positive and progesterone receptor-negative (er+/pr-) breast cancers account for 15% to 25% of all human breast cancers and display more aggressive malignant characteristics than er+/pr+ cancers. however, the molecular mechanism underlying development of er+/pr- breast cancers still remains elusive. we show here that tip30 deletion dramatically accelerated the onset of mammary tumors in the mmtv-neu mouse model of breast cancer. the mammary tumors arising in tip30(-/-)/mmtv-neu ... | 2010 | 21159643 |
| mineralocorticoid receptor mutations differentially affect individual gene expression profiles in pseudohypoaldosteronism type 1. | type 1 pseudohypoaldosteronism (pha1), a primary form of mineralocorticoid resistance, is due to inactivating mutations of the nr3c2 gene, coding for the mineralocorticoid receptor (mr). | 2010 | 21159846 |
| superantigens increase the survival of mice bearing t cell lymphomas by inducing apoptosis of neoplastic cells. | superantigens bind to major histocompatibility complex class ii molecules and interact with t cells expressing a particular t cell receptor vβ inducing a strong proliferation/deletion response of the superantigen-reactive t cells. however, there have been no attempts to investigate the ability of sags to induce apoptosis in neoplastic t cells by signaling through the vβ region of their tcr. in the present study we show that bacterial and mmtv-encoded superantigens induce the apoptosis of akr/j c ... | 2010 | 21203530 |
| identification and sequencing of a novel rodent gammaherpesvirus that establishes acute and latent infection in laboratory mice. | gammaherpesviruses encode numerous immunomodulatory molecules that contribute to their ability to evade the host immune response and establish persistent, lifelong infections. as the human gammaherpesviruses are strictly species specific, small animal models of gammaherpesvirus infection, such as murine gammaherpesvirus 68 (γhv68) infection, are important for studying the roles of gammaherpesvirus immune evasion genes in in vivo infection and pathogenesis. we report here the genome sequence and ... | 2011 | 21209105 |
| prevalent de novo somatic mutations in superantigen genes of mouse mammary tumor viruses in the genome of c57bl/6j mice and its potential implication in the immune system. | superantigens (sags) of mouse mammary tumor viruses (mmtvs) play a crucial role in t cell selection in the thymus in a t cell receptor (tcr) vβ-specific manner and sags presented by b cells activate t cells in the periphery. the peripheral t cell repertoire is dynamically shaped by the steady induction of t cell tolerance against self antigens throughout the lifespan. we hypothesize that de novo somatic mutation of endogenous mmtv sags contributes to the modulation of the peripheral t cell reper ... | 2011 | 21244697 |
| vital role for cd8+ cells in controlling retroviral infections. | antiviral adaptive immune defenses consist of humoral and cell-mediated responses, which together eliminate extracellular and intracellular virus. as most retrovirus-infected individuals do not raise efficient protective antivirus immune responses, the relative importance of humoral and cell-mediated responses in restraining retroviral infection is not well understood. we utilized retrovirus-resistant i/lnj mice, which control infection with mouse mammary tumor virus (mmtv) and murine leukemia v ... | 2011 | 21248041 |
| hdac activity is required for efficient core promoter function at the mouse mammary tumor virus promoter. | histone deacetylases (hdacs) have been shown to be required for basal or inducible transcription at a variety of genes by poorly understood mechanisms. we demonstrated previously that hdac inhibition rapidly repressed transcription from the mouse mammary tumor virus (mmtv) promoter by a mechanism that does not require the binding of upstream transcription factors. in the current study, we find that hdacs work through the core promoter sequences of mmtv as well as those of several cellular genes ... | 2010 | 21253530 |
| mmtv-cre transgenes can adversely affect lactation: considerations for conditional gene deletion in mammary tissue. | cre-loxp-mediated inactivation and activation of genes in mouse mammary epithelium have been widely used to study genetic pathways in normal development and neoplastic transformation in vivo. in 1997, we generated three distinct mouse lines carrying an identical mmtv-cre transgene (lines a, d, and f). because the presence of cre recombinase can adversely affect the physiology of nonmammary cells, we explored whether transgenic females display lactational defects. whereas dams from line d nurse t ... | 2011 | 21255551 |
| mouse mammary tumor virus molecular biology and oncogenesis. | mouse mammary tumor virus (mmtv), which was discovered as a milk-transmitted, infectious cancer-inducing agent in the 1930s, has been used since that time as an animal model for the study of human breast cancer. like other complex retroviruses, mmtv encodes a number of accessory proteins that both facilitate infection and affect host immune response. in vivo, the virus predominantly infects lymphocytes and mammary epithelial cells. high level infection of mammary epithelial cells ensures efficie ... | 2010 | 21274409 |
| prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer. | abstract: introduction: tumors that express estrogen receptor alpha (era+) comprise 75% of breast cancers in women. while treatments directed against this receptor have successfully lowered mortality rates, many primary tumors initially or later exhibit resistance. the paucity of murine models of this "luminal" tumor subtype has hindered studies of factors that promote their pathogenesis and modulate responsiveness to estrogen-directed therapeutics. since epidemiologic studies closely link prola ... | 2011 | 21276249 |
| singleminded-2s (sim2s) promotes delayed involution of the mouse mammary gland through suppression of stat3 and nf?b. | postlactational involution of the mammary gland provides a unique model to study breast cancer susceptibility and metastasis. we have shown that the short isoform of singleminded-2s (sim2s), a basic helix loop helix/pas transcription factor, plays a role in promoting lactogenic differentiation, as well as maintaining mammary epithelial differentiation and malignancy. sim2s is dynamically expressed during mammary gland development, with expression peaking during lactation, and decreasing in early ... | 2011 | 21292822 |
| identification of a gene-expression signature for predicting lymph node metastasis in patients with early stage cervical carcinoma. | pelvic lymph node metastasis (plnm) is an important prognostic factor for patients with cervical carcinoma. the objective of this study was to identify a gene-expression signature that could predict plnm in cervical carcinoma. | 2011 | 21319141 |
| regulatory t-cell expansion during chronic viral infection is dependent on endogenous retroviral superantigens. | regulatory t cells (treg) play critical roles in the modulation of immune responses to infectious agents. further understanding of the factors that control treg activation and expansion in response to pathogens is needed to manipulate treg function in acute and chronic infections. here we show that chronic, but not acute, infection of mice with lymphocytic choriomeningitis virus results in a marked expansion of foxp3(+) treg that is dependent on retroviral superantigen (sag) genes encoded in the ... | 2011 | 21321220 |
| evaluation of androgenic activity of nutraceutical-derived steroids using mammalian and yeast in vitro androgen bioassays. | androgenic steroids marketed online as nutraceuticals are a growing concern in sport doping. the inability of conventional mass spectrometry (ms)-based techniques to detect structurally novel androgens has led to the development of in vitro androgen bioassays to identify such designer androgens by their bioactivity. the objective of this study was to determine the androgenic bioactivity of novel steroidal compounds isolated from nutraceuticals using both yeast and mammalian cell-based androgen b ... | 2011 | 21329390 |
| mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models. | a human betaretrovirus resembling the mouse mammary tumor virus (mmtv) has been characterized in primary biliary cirrhosis (pbc) and associated with aberrant pyruvate dehydrogenase complex (pdc)-e2-like expression. as mmtv is prevalent in mice as either an exogenous or endogenous infection, we tested the hypothesis that mmtv is linked with anti-mitochondrial antibody (ama) production in models with severe immune dysfunction. | 2011 | 21334408 |
| mouse mammary tumor like virus sequences in breast milk from healthy lactating women. | mouse mammary tumor virus (mmtv) has been a long standing candidate as a potential cause of some human breast cancers. forty years ago, electron microscopic images of mmtv-like particles were identified in milk from 5% of healthy lactating women. these observations, however, have not been confirmed by modern methods. the purpose of this study was to confirm the presence of mmtv-like dna sequences in human milk from normal lactating women. standard and in situ pcr analyses were conducted on dna e ... | 2011 | 21365265 |
| loss of one tgfbr2 allele in fibroblasts promotes metastasis in mmtv: polyoma middle t transgenic and transplant mouse models of mammary tumor progression. | accumulation of fibroblasts is a phenomenon that significantly correlates with formation of aggressive cancers. while studies have shown that the tgf-ß signaling pathway is an important regulator of fibroblast activation, the functional contribution of tgf-ß signaling in fibroblasts during multi-step tumor progression remains largely unclear. in previous studies, we used a sub-renal capsule transplantation model to demonstrate that homozygous knockout of the tgfbr2 gene (tgbr2(fspko)) enhanced m ... | 2011 | 21374085 |
| transgenic animals and the study of cancer. | this chapter seeks to outline the strategies being employed to exploit transgenic mice as a tool in the study of cancer. rather than catalog the many different oncogene and oncogene-promoter combinations that have been introduced into transgenic mice to elicit tumors, i will concentrate on a single system that epitomizes the general approach. that system, pioneered by philip leder of harvard university, is mammary carcinogenesis induced by oncogene expression directed by the mouse mammary tumor ... | 1993 | 21390643 |
| loss of brca1 leads to an increase in epidermal growth factor receptor expression in mammary epithelial cells, and epidermal growth factor receptor inhibition prevents estrogen receptor-negative cancers in brca1-mutant mice. | abstract: introduction: women who carry a brca1 mutation typically develop "triple-negative" breast cancers (tnbc), defined by the absence of estrogen receptor (er), progesterone receptor and her2/neu. in contrast to er-positive tumors, tnbcs frequently express high levels of epidermal growth factor receptor (egfr). previously, we found a disproportionate fraction of progenitor cells in brca1 mutation carriers with egfr overexpression. here we examine the role of egfr in mammary epithelial cells ... | 2011 | 21396117 |
| a potential retroviral aetiology for mouse pbc: more answers or more questions? | | 2011 | 21396414 |
| transgenic expression of polyomavirus middle t antigen in the mouse prostate gives rise to carcinoma. | the middle t (mt) antigen of polyomavirus has provided fundamental insights into the regulation of mammalian cell growth in vitro and important animal models for the analysis of tumor induction. the mouse mammary tumor virus (mmtv)-mt model of breast cancer has been important for probing the cellular signaling pathways in mammary tumorigenesis. mt itself has no intrinsic enzymatic activity but, rather, transforms by binding to and activating key intracellular signaling molecules, phosphatidylino ... | 2011 | 21411524 |
| effects of intermittent and chronic calorie restriction on mammalian target of rapamycin (mtor) and igf-i signaling pathways in mammary fat pad tissues and mammary tumors. | chronic calorie restriction (ccr) prevents mammary tumor (mt) development in rodents. we reported that intermittent calorie restriction (icr) provides greater protection than ccr in mmtv-tgf-α mice. the mammalian target of rapamycin (mtor) pathway is involved in mt development. here the impact of icr versus ccr on proteins associated with mtor signaling in mammary tissues and mts from mmtv-tgf-α mice was determined. mice were enrolled at 10 wk of age into ad libitum-fed (al), ccr, and icr groups ... | 2011 | 21462085 |