| a bioluminescence reporter mouse that monitors expression of constitutively active β-catenin. | this short technical report describes the generation and characterization of a bioluminescence reporter mouse that is engineered to detect and longitudinally monitor the expression of doxycycline-induced constitutively active β-catenin. the new responder transgenic mouse contains the teto-δn89β-cattmila transgene, which consists of the tet-operator followed by a bicistronic sequence encoding a stabilized form of active β-catenin (δn89β-catenin), an internal ribosome entry site, and the firefly l ... | 2017 | 28253313 |
| mmtv-pymt and derived met-1 mouse mammary tumor cells as models for studying the role of the androgen receptor in triple-negative breast cancer progression. | triple-negative breast cancer (tnbc) has a faster rate of metastasis compared to other breast cancer subtypes, and no effective targeted therapies are currently fda-approved. recent data indicate that the androgen receptor (ar) promotes tumor survival and may serve as a potential therapeutic target in tnbc. studies of ar in disease progression and the systemic effects of anti-androgens have been hindered by the lack of an ar-positive (ar+) immunocompetent preclinical model. in this study, we ide ... | 2017 | 28194662 |
| high folic acid diet enhances tumour growth in pymt-induced breast cancer. | the b-vitamin folate is among the most studied bioactive food compound, and a dietary intake meeting the daily requirements has been found to reduce the risk of cancer and cardiovascular diseases as well as preventing neural tube defects during fetal development. several countries have therefore introduced dietary fortification with folic acid. however, clinical and animal studies suggest that folic acid has a dual role in cancer development. | 2017 | 28152548 |
| novel adenovirus encoded virus-like particles displaying the placental malaria associated var2csa antigen. | the malaria parasite plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. the var2csa mediated binding to a distinct chondroitin sulphate a (csa) is a crucial step in the pathophysiology of placental malaria and the csa binding region of var2csa has been identified as a promising vaccine target against placental malaria. here we designed adenovirus encoded virus-like particles (vlp) by co-encoding simian immu ... | 2017 | 28131394 |
| atrial natriuretic peptide regulates adipose tissue accumulation in adult atria. | the abundance of epicardial adipose tissue (eat) is associated with atrial fibrillation (af), the most frequent cardiac arrhythmia. however, both the origin and the factors involved in eat expansion are unknown. here, we found that adult human atrial epicardial cells were highly adipogenic through an epithelial-mesenchymal transition both in vitro and in vivo. in a genetic lineage tracing the wt1(creert2+/-)rosa(tdt+/-) mouse model subjected to a high-fat diet, adipocytes of atrial eat derived f ... | 2017 | 28096344 |
| β-catenin haploinsufficiency promotes mammary tumorigenesis in an erbb2-positive basal breast cancer model. | aberrant activation of β-catenin through its activity as a transcription factor has been observed in a large proportion of human malignancies. despite the improved understanding of the β-catenin signaling pathway over the past three decades, attempts to develop therapies targeting β-catenin remain challenging, and none of these targeted therapies have advanced to the clinic. in this study, we show that part of the challenge in antagonizing β-catenin is caused by its dual functionality as a cell ... | 2017 | 28096336 |
| ccl2-driven inflammation increases mammary gland stromal density and cancer susceptibility in a transgenic mouse model. | macrophages play diverse roles in mammary gland development and breast cancer. cc-chemokine ligand 2 (ccl2) is an inflammatory cytokine that recruits macrophages to sites of injury. although ccl2 has been detected in human and mouse mammary epithelium, its role in regulating mammary gland development and cancer risk has not been explored. | 2017 | 28077158 |
| mouse mammary tumor-like virus (mmtv) is present in human breast tissue before development of virally associated breast cancer. | there is substantial evidence that a virus homologous to mouse mammary tumor virus (mmtv) may have a role in human breast cancer. the present study indicates that those who developed breast cancer associated with an mmtv-like virus had this virus in their non-cancerous breast tissues years before the cancer developed. | 2017 | 28053656 |
| disease subtype-independent biomarkers of breast cancer chemoprevention by the ayurvedic medicine phytochemical withaferin a. | a nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. the present study was undertaken to determine the efficacy of an ayurvedic medicine phytochemical (withaferin a, [wa]) for chemoprevention of breast cancer and to elucidate its mode of action. | 2017 | 28040797 |
| hic-5 remodeling of the stromal matrix promotes breast tumor progression. | the remodeling of the stromal extracellular matrix (ecm) has a crucial, but incompletely understood role during tumor progression and metastasis. hic-5, a focal adhesion scaffold protein, has previously been implicated in tumor cell invasion, proliferation and metastasis. to investigate the role of hic-5 in breast tumor progression in vivo, hic-5(-/-) mice were generated and crossed with the mouse mammary tumor virus-polyoma middle t-antigen mouse. tumors from the hic-5(-/-);pymt mice exhibited ... | 2016 | 27893716 |
| inherently variable responses to glucocorticoid stress among endogenous retroviruses isolated from 23 mouse strains. | active participation of endogenous retroviruses (ervs) in disease processes has been exemplified by the finding that the herv (human erv)-w envelope protein is involved in the pathogenesis of multiple sclerosis, an autoimmune disease. we also demonstrated that injury-elicited stressors alter the expression of murine ervs (muervs), both murine leukemia virus-type and mouse mammary tumor virus (mmtv)-type (mmtv-muerv). in this study, to evaluate mmtv-muervs' responses to stress (e.g., injury, infe ... | 2016 | 27816520 |
| tissue-selective expression of a conditionally-active rock2-estrogen receptor fusion protein. | the serine/threonine kinases rock1 and rock2 are central mediators of actomyosin contractile force generation that act downstream of the rhoa small gtp-binding protein. as a result, they have key roles in regulating cell morphology and proliferation, and have been implicated in numerous pathological conditions and diseases including hypertension and cancer. here we describe the generation of a gene-targeted mouse line that enables cre-inducible expression of a conditionally-active fusion between ... | 2016 | 27775859 |
| discovery of klotho peptide antagonists against wnt3 and wnt3a target proteins using combination of protein engineering, protein-protein docking, peptide docking and molecular dynamics simulations. | the klotho is known as lifespan enhancing protein involved in antagonizing the effect of wnt proteins. wnt proteins are stem cell regulators, and uninterrupted exposure of wnt proteins to the cell can cause stem and progenitor cell senescence, which may lead to aging. keeping in mind the importance of klotho in wnt signaling, in silico approaches have been applied to study the important interactions between klotho and wnt3 and wnt3a (wingless-type mouse mammary tumor virus (mmtv) integration sit ... | 2017 | 27766889 |
| 4-hpr impairs bladder cancer cell migration and invasion by interfering with the wnt5a/jnk and wnt5a/mmp-2 signaling pathways. | in order to identify the anti-invasive and anti-metastatic effect of the synthetic retinoid n-(4-hydroxyphenyl) retinamide (4-hpr) on the human bladder cancer ej cell line, and to study its impact on the expression of wingless-type mouse mammary tumor virus integration site family, member 5a (wnt5a), the phosphorylation of c-jun n-terminal kinase (jnk), the expression levels of matrix metalloproteinase-2 (mmp-2), and the migration and invasion of ej cells, migration and matrigel invasion assays, ... | 2016 | 27602114 |
| wnt signaling in regulation of biological functions of the nurse cell harboring trichinella spp. | the nurse cell (nc) constitutes in mammalian skeletal muscles a confined intracellular niche to support the metabolic needs of muscle larvae of trichinella spp. encapsulating species. the main biological functions of nc were identified as hypermitogenic growth arrest and pro-inflammatory phenotype, both inferred to depend on ap-1 (activator protein 1) transcription factor. since those functions, as well as ap-1 activity, are known to be regulated among other pathways, also by wnt (wingless-type ... | 2016 | 27589866 |
| protein tyrosine phosphatase 1b inhibitors from the stems of akebia quinata. | ptp1b deficiency in mouse mammary tumor virus (mmtv)-neunt transgenic mice inhibited the onset of mmtv-neunt-evoked breast cancer, while its overexpression was observed in breast cancer. thus, ptp1b inhibitors are considered chemopreventative agents for breast cancer. as part of our program to find ptp1b inhibitors, one new diterpene glycoside (1) and 13 known compounds (2-14) were isolated from the methanol extract of the stems of akebia quinata. all isolates were identified based on extensive ... | 2016 | 27548130 |
| rank signaling blockade reduces breast cancer recurrence by inducing tumor cell differentiation. | rank expression is associated with poor prognosis in breast cancer even though its therapeutic potential remains unknown. rankl and its receptor rank are downstream effectors of the progesterone signaling pathway. however, rank expression is enriched in hormone receptor negative adenocarcinomas, suggesting additional roles for rank signaling beyond its hormone-dependent function. here, to explore the role of rank signaling once tumors have developed, we use the mouse mammary tumor virus-polyoma ... | 2016 | 27480274 |
| inhibitor of dna binding 1 regulates cell cycle progression of endothelial progenitor cells through induction of wnt2 expression. | endothelial injury is a risk factor for atherosclerosis. endothelial progenitor cell (epc) proliferation contributes to vascular injury repair. overexpression of inhibitor of dna binding 1 (id1) significantly promotes epc proliferation; however, the underlying molecular mechanism remains to be fully elucidated. the present study investigated the role of id1 in cell cycle regulation of epcs, which is closely associated with proliferation. overexpression of id1 increased the proportion of epcs in ... | 2016 | 27432753 |
| metabolic history impacts mammary tumor epithelial hierarchy and early drug response in mice. | the emerging links between breast cancer and metabolic dysfunctions brought forth by the obesity pandemic predict a disproportionate early disease onset in successive generations. moreover, sensitivity to chemotherapeutic agents may be influenced by the patient's metabolic status that affects the disease outcome. maternal metabolic stress as a determinant of drug response in progeny is not well defined. here, we evaluated mammary tumor response to doxorubicin in female mouse mammary tumor virus- ... | 2016 | 27402613 |
| non-metabolisable insulin glargine does not promote breast cancer growth in a mouse model of type 2 diabetes. | previous epidemiological studies have reported a potential link between insulin analogues and breast cancer; however, a prospective randomised controlled trial showed neutral effects of insulin glargine on cancer risk. insulin glargine is metabolised in vivo to an m1 metabolite. a question remains whether a subset of individuals with slower rates of glargine metabolism or who are on high doses could, theoretically, have an increased risk of cancer progression if a tumour is already present. in t ... | 2016 | 27241182 |
| charged amino acid-rich leucine zipper-1 (crlz-1) as a target of wnt signaling pathway controls pre-b cell proliferation by affecting runx/cbfβ-targeted vpreb and λ5 genes. | the proliferation of pre-b cells is known to further increase the clonal diversity of b cells at the stage of pre-b cells by allowing the same rearranged heavy chains to combine with differently rearranged light chains in a subsequent developmental stage. crlz-1 (charged amino acid-rich leucine zipper-1) was found to control this proliferation of pre-b cells by working as a wnt (wingless-related mouse mammary tumor virus integration site) target gene in these cells. mechanistically, crlz-1 prote ... | 2016 | 27226553 |
| neutrophils drive accelerated tumor progression in the collagen-dense mammary tumor microenvironment. | high mammographic density has been correlated with a 4-fold to 6-fold increased risk of developing breast cancer, and is associated with increased stromal deposition of extracellular matrix proteins, including collagen i. the molecular and cellular mechanisms responsible for high breast tissue density are not completely understood. | 2016 | 27169366 |
| molecular cloning, characterization and expression analysis of wnt4, wnt5, wnt6, wnt7, wnt10 and wnt16 from litopenaeus vannamei. | the wnt (wg-type mmtv integration site) signaling represents as the negative regulator of virus-induced innate immune responses. wnt genes act as ligands to activate the wnt signaling. to know more about the information of wnt genes in invertebrates, litopenaeus vannamei wnt genes (lvwnts) were identified and characterized. in this study, six wnt genes (lvwnt4, lvwnt5, lvwnt6, lvwnt7, lvwnt10 and lvwnt16) were obtained in l. vannamei. the complete cdnas open reading frames (orf) of lvwnt4, lvwnt ... | 2016 | 27153750 |
| tumoral vitamin d synthesis by cyp27b1 1-α-hydroxylase delays mammary tumor progression in the pymt-mmtv mouse model and its action involves nf-κb modulation. | biologically active vitamin d (1,25-dihydroxycholecalciferol or 1,25(oh)2d) is synthetized from inactive prohormone 25-hydroxycholecalciferol (25(oh)d) by the enzyme cyp27b1 1-α-hydroxylase in kidney and several extrarenal tissues including breast. although the development of breast cancer has been linked to inadequate vitamin d status, the importance of bioactive vitamin d production within tumors themselves is not fully understood. to investigate the role of tumoral vitamin d production in mam ... | 2016 | 27119753 |
| lessons learned from mouse mammary tumor virus in animal models. | mouse mammary tumor virus (mmtv), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. the main target cells for mmtv infection in vivo are cells of the immune system and mammary epithelial cells. although the host mounts an immune response to the virus, mmtv has evolved multiple means of evading this r ... | 2016 | 27034391 |
| genome-wide analysis of dna methylation and gene expression defines molecular characteristics of crohn's disease-associated fibrosis. | fibrosis of the intestine is a common and poorly understood complication of crohn's disease (cd) characterized by excessive deposition of extracellular matrix and accompanied by narrowing and obstruction of the gut lumen. defining the molecular characteristics of this fibrotic disorder is a vital step in the development of specific prediction, prevention, and treatment strategies. previous epigenetic studies indicate that alterations in dna methylation could explain the mechanism by which mesenc ... | 2016 | 26973718 |
| polypyrimidine tract-binding protein binds to the 5' untranslated region of the mouse mammary tumor virus mrna and stimulates cap-independent translation initiation. | the 5' untranslated region (utr) of the full-length mrna of the mouse mammary tumor virus (mmtv) harbors an internal ribosomal entry site (ires). in this study, we show that the polypyrimidine tract-binding protein (ptb), an rna-binding protein with four rna recognition motifs (rrms), binds to the mmtv 5' utr stimulating its ires activity. there are three isoforms of ptb: ptb1, ptb2, and ptb4. results show that ptb1 and ptb4, but not ptb2, stimulate mmtv-ires activity. ptb1 promotes mmtv-ires-me ... | 2016 | 26972759 |
| a new immunization and treatment strategy for mouse mammary tumor virus (mmtv) associated cancers. | mouse mammary tumor virus (mmtv) causes mammary carcinoma or lymphoma in mice. an increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. it is thus of importance to develop new strategies to impair the development, growth and metastasis of mmtv-associated cancers. the signal peptide of the envelope precursor protein of this virus: mmtv-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular ... | 2016 | 26934560 |
| expression of a dominant t-cell receptor can reduce toxicity and enhance tumor protection of allogeneic t-cell therapy. | due to the lack of specificity for tumor antigens, allogeneic t-cell therapy is associated with graft-versus-host disease. enhancing the anti-tumor specificity while reducing the graft-versus-host disease risk of allogeneic t cells has remained a research focus. in this study, we demonstrate that the introduction of 'dominant' t-cell receptors into primary murine t cells can suppress the expression of endogenous t-cell receptors in a large proportion of the gene-modified t cells. adoptive transf ... | 2016 | 26802053 |
| x-ray structure of the mmtv-a nucleosome core. | the conformation of dna bound in nucleosomes depends on the dna sequence. questions such as how nucleosomes are positioned and how they potentially bind sequence-dependent nuclear factors require near-atomic resolution structures of the nucleosome core containing different dna sequences; despite this, only the dna for two similar α-satellite sequences and a sequence (601) selected in vitro have been visualized bound in the nucleosome core. here we report the 2.6-å resolution x-ray structure of a ... | 2016 | 26787910 |
| genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains. | laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of "conventional" genes and/or microsatellites in the absence of a single completely sequenced mouse genome. first, we examined variations in the genomic landscapes of transposable repetitive el ... | 2016 | 26779669 |
| pmca2 regulates her2 protein kinase localization and signaling and promotes her2-mediated breast cancer. | in the lactating mammary gland, the plasma membrane calcium atpase2 (pmca2) transports milk calcium. its expression is activated in breast cancers, where high tumor levels predict increased mortality. we find that pmca2 expression correlates with her2 levels in breast cancers and that pmca2 interacts with her2 in specific actin-rich membrane domains. knocking down pmca2 increases intracellular calcium, disrupts interactions between her2 and hsp-90, inhibits her2 signaling, and results in interna ... | 2016 | 26729871 |
| wnt4 coordinates directional cell migration and extension of the müllerian duct essential for ontogenesis of the female reproductive tract. | the müllerian duct (md) is the anlage of the oviduct, uterus and upper part of the vagina, the main parts of the female reproductive tract. several wingless-type mouse mammary tumor virus (mmtv) integration site family member (wnt) genes, including wnt4, wnt5a and wnt7a, are involved in the development of md and its derivatives, with wnt4 particularly critical, since the md fails to develop in its absence. we use, here, wnt4(egfpcre)-based fate mapping to demonstrate that the md tip cells and th ... | 2016 | 26721931 |
| elf5 drives lung metastasis in luminal breast cancer through recruitment of gr1+ cd11b+ myeloid-derived suppressor cells. | during pregnancy, the ets transcription factor elf5 establishes the milk-secreting alveolar cell lineage by driving a cell fate decision of the mammary luminal progenitor cell. in breast cancer, elf5 is a key transcriptional determinant of tumor subtype and has been implicated in the development of insensitivity to anti-estrogen therapy. in the mouse mammary tumor virus-polyoma middle t (mmtv-pymt) model of luminal breast cancer, induction of elf5 levels increased leukocyte infiltration, angioge ... | 2015 | 26717410 |
| differentiation of mammary tumors and reduction in metastasis upon malat1 lncrna loss. | genome-wide analyses have identified thousands of long noncoding rnas (lncrnas). malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncrnas whose expression is altered in numerous cancers. here we report that genetic loss or systemic knockdown of malat1 using antisense oligonucleotides (asos) in the mmtv (mouse mammary tumor virus)-pymt mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumor ... | 2016 | 26701265 |
| wnt5a is required for normal ovarian follicle development and antagonizes gonadotropin responsiveness in granulosa cells by suppressing canonical wnt signaling. | whereas the roles of the canonical wingless-type mmtv (mouse mammary tumor virus) integration site family (wnt) signaling pathway in the regulation of ovarian follicle growth and steroidogenesis are now established, noncanonical wnt signaling in the ovary has been largely overlooked. noncanonical wnts, including wnt5a and wnt11, are expressed in granulosa cells (gcs) and are differentially regulated throughout follicle development, but their physiologic roles remain unknown. using conditional ge ... | 2016 | 26667040 |
| aberrant gli1 activation in dna damage response, carcinogenesis and chemoresistance. | the canonical hedgehog (hh) pathway is a multicomponent signaling cascade (hh, protein patched homolog 1 (ptch1), smoothened (smo)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (gli1), gli2 and gli3. activation of glis must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. however, dysregulation ... | 2015 | 26633513 |
| expression of wingless-type mouse mammary tumor virus integration site family pathway effectors in lymphatic and hepatic metastases of patients with colorectal cancer: associations with the primary tumor. | the wingless-type mouse mammary tumor virus integration site family (wnt) pathway plays a major role in the carcinogenesis of colorectal cancer (crc). its most important effector, the nuclear β-catenin, influences not only transcription but also the proliferation and dedifferentiation of the colonic mucosa. this induces an epithelial-mesenchymal transition which ultimately can lead to the development of cancer and the formation of metastases. however, little is known about the exact interaction ... | 2015 | 26622584 |
| whole-transcriptome analysis of mouse adipose tissue in response to short-term caloric restriction. | caloric restriction (cr) has been shown to extend the lifespan of many species by improving cellular function and organismal health. additionally, fat reduction by cr may play an important role in lengthening lifespan and preventing severe age-related diseases. interestingly, cr induced the greatest transcriptome change in the epididymal fat of mice in our study. in this transcriptome analysis, we identified and categorized 446 genes that correlated with cr level. we observed down-regulation of ... | 2016 | 26606930 |
| osteoblast-specific overexpression of human wnt16 increases both cortical and trabecular bone mass and structure in mice. | previous genome-wide association studies have identified common variants in genes associated with bone mineral density (bmd) and risk of fracture. recently, we identified single nucleotide polymorphisms (snps) in wingless-type mouse mammary tumor virus integration site (wnt)16 that were associated with peak bmd in premenopausal women. to further identify the role of wnt16 in bone mass regulation, we created transgenic (tg) mice overexpressing human wnt16 in osteoblasts. we compared bone phenotyp ... | 2016 | 26584014 |
| evaluation frequency of merkel cell polyoma, epstein-barr and mouse mammary tumor viruses in patients with breast cancer in kerman, southeast of iran. | breast cancer is the most common cancer among women worldwide. roles of the epstein-barr, merkel cell polyoma and mouse mammary tumor viruses in breast carcinogenesis are still controversial although any relationship would clearly be important for breast cancer etiology, early detection and prevention. in the present study associations between ebv, mmtv and merkel cell polyoma virus and breast cancer in 100 iranian patients were evaluated using paraffin-embedded tissues. eber rna and expression ... | 2015 | 26514536 |
| mda-7/il-24 functions as a tumor suppressor gene in vivo in transgenic mouse models of breast cancer. | melanoma differentiation associated gene-7/interleukin-24 (mda-7/il-24) is a novel member of the il-10 gene family that selectively induces apoptosis and toxic autophagy in a broad spectrum of human cancers, including breast cancer, without harming normal cells or tissues. the ability to investigate the critical events underlying cancer initiation and progression, as well as the capacity to test the efficacy of novel therapeutics, has been significantly advanced by the development of genetically ... | 2015 | 26474456 |
| mammalian lipopolysaccharide receptors incorporated into the retroviral envelope augment virus transmission. | the orally transmitted retrovirus mouse mammary tumor virus (mmtv) requires the intestinal microbiota for persistence. virion-associated lipopolysaccharide (lps) activates toll-like receptor 4 (tlr4), stimulating production of the immunosuppressive cytokine il-10 and mmtv evasion of host immunity. however, the mechanisms by which mmtv associates with lps remain unknown. we find that the viral envelope contains the mammalian lps-binding factors cd14, tlr4, and md-2, which, in conjunction with lps ... | 2015 | 26468748 |
| mitochondrial mass, a new metabolic biomarker for stem-like cancer cells: understanding wnt/fgf-driven anabolic signaling. | here, we developed an isogenic cell model of "stemness" to facilitate protein biomarker discovery in breast cancer. for this purpose, we used knowledge gained previously from the study of the mouse mammary tumor virus (mmtv). mmtv initiates mammary tumorigenesis in mice by promoter insertion adjacent to two main integration sites, namely int-1 (wnt1) and int-2 (fgf3), which ultimately activates wnt/β-catenin signaling, driving the propagation of mammary cancer stem cells (cscs). thus, to develop ... | 2015 | 26421711 |
| loss of sfrp4 alters body size, food intake, and energy expenditure in diet-induced obese male mice. | secreted frizzled-related protein 4 (sfrp4) is an extracellular regulator of the wingless-type mouse mammary tumor virus integration site family (wnt) pathway. sfrp4 has been implicated in adipocyte dysfunction, obesity, insulin resistance, and impaired insulin secretion in patients with type 2 diabetes. however, the exact role of sfrp4 in regulating whole-body metabolism and glucose homeostasis is unknown. we show here that male sfrp4(-/-) mice have increased spine length and gain more weight w ... | 2015 | 26406932 |
| no evidence of antibodies against gad65 and other specific antigens in children with autism. | the presence of autoantibodies has been proposed as evidence for a role of autoimmunity in autism. this report investigates the prevalence of autoantibodies in children with autism using the luciferase immunoprecipitation systems (lips) immunoassay technology. a panel of autoantibody targets against several known and candidate neurological autoantigens, autoimmune-associated autoantigens and viruses was employed. | 2015 | 26366376 |
| heregulin co-opts pr transcriptional action via stat3 role as a coregulator to drive cancer growth. | accumulated findings have demonstrated the presence of bidirectional interactions between progesterone receptor (pr) and the erbb family of receptor tyrosine kinases signaling pathways in breast cancer. we previously revealed signal transducer and activator of transcription 3 (stat3) as a nodal convergence point between said signaling pathways proving that stat3 is activated by one of the erbbs' ligands, heregulin (hrg)β1 via erbb2 and through the co-option of pr as a signaling molecule. here, w ... | 2015 | 26340407 |
| contrast-enhanced x-ray detection of microcalcifications in radiographically dense mammary tissue using targeted gold nanoparticles. | breast density reduces the accuracy of mammography, motivating methods to improve sensitivity and specificity for detecting abnormalities within dense breast tissue, but preclinical animal models are lacking. therefore, the objectives of this study were to investigate a murine model of radiographically dense mammary tissue and contrast-enhanced x-ray detection of microcalcifications in dense mammary tissue by targeted delivery of bisphosphonate-functionalized gold nanoparticles (bp-au nps). mamm ... | 2015 | 26308767 |
| phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. | melanoma is difficult to treat once it becomes metastatic. however, the precise ancestral relationship between primary tumors and their metastases is not well understood. we performed whole-exome sequencing of primary melanomas and multiple matched metastases from eight patients to elucidate their phylogenetic relationships. in six of eight patients, we found that genetically distinct cell populations in the primary tumor metastasized in parallel to different anatomic sites, rather than sequenti ... | 2015 | 26286987 |
| protein tyrosine kinase 6 promotes erbb2-induced mammary gland tumorigenesis in the mouse. | protein tyrosine kinase 6 (ptk6) expression, activation, and amplification of the ptk6 gene have been reported in erbb2/her2-positive mammary gland cancers. to explore contributions of ptk6 to mammary gland tumorigenesis promoted by activated erbb2, we crossed ptk6-/- mice with the mouse mammary tumor virus-erbb2 transgenic mouse line expressing activated erbb2 and characterized tumor development and progression. erbb2-induced tumorigenesis was significantly delayed and diminished in mice lackin ... | 2015 | 26247733 |
| thalamic wnt3 secretion spatiotemporally regulates the neocortical ribosome signature and mrna translation to specify neocortical cell subtypes. | neocortical development requires tightly controlled spatiotemporal gene expression. however, the mechanisms regulating ribosomal complexes and the timed specificity of neocortical mrna translation are poorly understood. we show that active mrna translation complexes (polysomes) contain ribosomal protein subsets that undergo dynamic spatiotemporal rearrangements during mouse neocortical development. ribosomal protein specificity within polysome complexes is regulated by the arrival of in-growing ... | 2015 | 26245956 |
| human saliva as route of inter-human infection for mouse mammary tumor virus. | etiology of human breast cancer is unknown, whereas the mouse mammary tumor virus (mmtv) is recognized as the etiologic agent of mouse mammary carcinoma. moreover, this experimental model contributed substantially to our understanding of many biological aspects of the human disease. several data strongly suggest a causative role of mmtv in humans, such as the presence of viral sequences in a high percentage of infiltrating breast carcinoma and in its preinvasive lesions, the production of viral ... | 2015 | 26214095 |
| deletion of the amino acid transporter slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer. | slc6a14 mediates na(+)/cl(-)-coupled concentrative uptake of a broad-spectrum of amino acids. it is expressed at low levels in many tissues but up-regulated in certain cancers. pharmacological blockade of slc6a14 causes amino acid starvation in estrogen receptor positive (er+) breast cancer cells and suppresses their proliferation in vitro and in vivo. in the present study, we interrogated the role of this transporter in breast cancer by deleting slc6a14 in mice and monitoring the consequences o ... | 2015 | 26173258 |
| recombinant human granulocyte colony-stimulating factor promotes preinvasive and invasive estrogen receptor-positive tumor development in mmtv-erbb2 mice. | we investigated whether recombinant human granulocyte colony-stimulating factor (rhg-csf) could promote the development of preinvasive and invasive breast cancer in mouse mammary tumor virus (mmtv-erbb2) mice with estrogen receptor-positive tumors. | 2015 | 26155288 |
| endogenization of mouse mammary tumor virus (mmtv)-like elements in genomes of pikas (ochotona sp.). | despite the finding in european rabbit and other leporid genomes of the first ever described endogenous lentivirus and of a european rabbit exclusive endogenous gammaretrovirus, until now no exogenous retroviruses have been isolated in lagomorpha species. nevertheless, looking for the presence of endogenous retroviruses (ervs) in the species genomes could lead to the discovery of retroviral lineages yet to be found in lagomorpha. different mammalian genomes harbor endogenous viral sequences phyl ... | 2015 | 26151606 |
| the role of wnt signaling in adult ovarian folliculogenesis. | wingless-type mouse mammary tumor virus integration site (wnt) signaling molecules are locally secreted glycoproteins that play important role in regulation of ovarian follicle maturation and steroid production. components of the wnt signaling pathway have been demonstrated to impact reproductive functions, including embryonic development of the sex organs and regulation of follicle maturation controlling steroidogenesis in the postnatal ovary. emerging evidence underscores the complexity of wnt ... | 2015 | 26130815 |
| pericentriolar targeting of the mouse mammary tumor virus gag protein. | the gag protein of the mouse mammary tumor virus (mmtv) is the chief determinant of subcellular targeting. electron microscopy studies show that mmtv gag forms capsids within the cytoplasm and assembles as immature particles with mmtv rna and the y box binding protein-1, required for centrosome maturation. other betaretroviruses, such as mason-pfizer monkey retrovirus (m-pmv), assemble adjacent to the pericentriolar region because of a cytoplasmic targeting and retention signal in the matrix pro ... | 2015 | 26121257 |
| presence of insulin-like growth factor binding proteins correlates with tumor-promoting effects of matrix metalloproteinase 9 in breast cancer. | the stroma of breast cancer can promote the disease's progression, but whether its composition and functions are shared among different subtypes is poorly explored. we compared stromal components of a luminal [mouse mammary tumor virus (mmtv)-neu] and a triple-negative/basal-like [c3(1)-simian virus 40 large t antigen (tag)] genetically engineered breast cancer mouse model. the types of cytokines and their expression levels were very different in the two models, as was the extent of innate immun ... | 2015 | 26025665 |
| structural dynamics and inhibitor searching for wnt-4 protein using comparative computational studies. | wnt-4 (wingless mouse mammary tumor virus integration site-4) protein is involved in many crucial embryonic pathways regulating essential processes. aberrant wnt-4 activity causes various anomalies leading to gastric, colon, or breast cancer. wnt-4 is a conserved protein in structure and sequence. all wnt proteins contain an unusual fold comprising of a thumb (or n-terminal domain) and index finger (or c-terminal domain) bifurcated by a palm domain. the aim of this study was to identify the best ... | 2015 | 25995617 |
| single amino acid substitution (g42e) in the receptor binding domain of mouse mammary tumour virus envelope protein facilitates infection of non-murine cells in a transferrin receptor 1-independent manner. | mouse mammary tumour virus (mmtv) is a betaretrovirus that infects rodent cells and uses mouse tranferrin receptor 1 (tfr1) for cell entry. several mmtv strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. furthermore, there have been reports that the continued passage of mmtv in heterologous cell lines gives rise to novel variants that are able to infect naive non- ... | 2015 | 25980759 |
| pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in mmtv-pymt transgenic mice. | matrix metalloproteinase-8 (mmp-8; neutrophil collagenase) is an important regulator of innate immunity that has oncosuppressive actions in numerous tumor types. | 2015 | 25848906 |
| int6 reduction activates stromal fibroblasts to enhance transforming activity in breast epithelial cells. | the int6 gene was first discovered as a site of integration in mouse mammary tumors by the mouse mammary tumor virus; however, int6's role in the development of human breast cancer remains largely unknown. by gene silencing, we have previously shown that repressing int6 promotes transforming activity in untransformed human mammary epithelial cells. in the present study, guided by microarray data of human tumors, we have discovered a role of int6 in stromal fibroblasts. | 2015 | 25774287 |
| 2-aryl-3-methyloctahydrophenanthrene-2,3,7-triols as potent dissociated glucocorticoid receptor agonists. | a significant improvement in agonist activity of the previously described 2-aryloctahydrophenanthrene-2,3,7-triol series of dissociated glucocorticoid receptor agonists (dagrs) was achieved by modifying the substitution at c3 from (s)-3-hydroxy to (r)-3-hydroxy-3-methyl. the ic50 of the prototype 13 in the efficacy assay measuring repression of il-1 induced mmp-13 expression was 3.5 nm, exhibiting 87% of the maximal effect of dexamethasone (dex). it displayed a dissociated profile by exhibiting ... | 2015 | 25706100 |
| targeting the hsp70 gene delays mammary tumor initiation and inhibits tumor cell metastasis. | elevated levels of the inducible heat-shock protein 70 (hsp72) have been implicated in mammary tumorigenesis in histological investigations of human breast cancer. we therefore examined the role of hsp72 in mice, using animals in which the hsp70 gene was inactivated. we used a spontaneous tumor system with mice expressing the polyomavirus middle t (pymt) oncogene under control of the mouse mammary tumor virus (mmtv) long-terminal repeat (mmt mice). these mice developed spontaneous, metastatic ma ... | 2015 | 25659585 |
| the breast cancer susceptibility fgfr2 provides an alternate mode of her2 activation. | fibroblast growth factor receptor 2 (fgfr2) has been shown reproducibly in genome-wide association studies to be associated with increased breast cancer risk. here we show that mouse mammary tumor virus-neu mice develop breast carcinomas with fgfr2 immunoreactivity that parallels her2 expression. fgfr2 signaling promotes her2 shedding through the metalloprotease adam10 leading to intracellular accumulation of the truncated p95her2 protein. this is accompanied by enhanced her2 signaling and dimin ... | 2015 | 25639874 |
| loss of periostin/osf-2 in erbb2/neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced notch1 activity. | periostin (postn) is a secreted cell adhesion protein that activates signaling pathways to promote cancer cell survival, angiogenesis, invasion, and metastasis. interestingly, postn is frequently overexpressed in numerous human cancers, including breast, lung, colon, pancreatic, and ovarian cancer. | 2015 | 25592291 |
| overexpression of erbb4 jm-a cyt-1 and cyt-2 isoforms in transgenic mice reveals isoform-specific roles in mammary gland development and carcinogenesis. | human epidermal growth factor receptor (erbb4/her4) belongs to the epidermal growth factor receptor/erbb family of receptor tyrosine kinases. while erbb1, erbb2 and erbb3 are often overexpressed or activated in breast cancer, and are oncogenic, the role of erbb4 in breast cancer is uncertain. some studies suggest a tumor suppressor role of erbb4, while other reports suggest an oncogenic potential. alternative splicing of erbb4 yields four major protein products, these spliced isoforms differ in ... | 2014 | 25516216 |
| prevalence of hmtv in breast carcinomas and unaffected tissue from mexican women. | breast cancer is a complex multifactorial genetic disease. among other factors, race and, to an even greater extent, viruses are known to influence the development of this heterogeneous disease. it has been reported that mmtv-like (hmtv) gene sequences with a 90 to 98% homology to mouse mammary tumor virus are found in several populations with a prevalence range of 0 to 74%. in the mexican population, 4.2% of patients with breast cancer exhibit the presence of hmtv (mmtv-like) sequences. the aim ... | 2014 | 25495285 |
| c3h strain of mouse mammary tumour virus, like gr strain, infects human mammary epithelial cells, albeit less efficiently than murine mammary epithelial cells. | mouse mammary tumour virus (mmtv) is a member of the genus betaretrovirus, infects rodent cells and uses mouse tranferrin receptor 1 for cell entry. several mmtv strains have been shown to productively infect, in addition to murine cells, various heterologous cell lines including those of human origin, albeit less efficiently than murine cells. here, we analysed whether mmtv from c3h mice [mmtv(c3h)], reported previously to be incapable of infecting human cells, could productively infect human c ... | 2015 | 25491421 |
| autophagy regulator becn1 suppresses mammary tumorigenesis driven by wnt1 activation and following parity. | earlier studies reported allelic deletion of the essential autophagy regulator becn1 in breast cancers implicating becn1 loss, and likely defective autophagy, in tumorigenesis. recent studies have questioned the tumor suppressive role of autophagy, as autophagy-related gene (atg) defects generally suppress tumorigenesis in well-characterized mouse tumor models. we now report that, while it delays or does not alter mammary tumorigenesis driven by palb2 loss or erbb2 and pymt overexpression, monoa ... | 2014 | 25483966 |
| intratumoral heterogeneity: clonal cooperation in epithelial-to-mesenchymal transition and metastasis. | although phenotypic intratumoral heterogeneity was first described many decades ago, the advent of next-generation sequencing has provided conclusive evidence that in addition to phenotypic diversity, significant genotypic diversity exists within tumors. tumor heterogeneity likely arises both from clonal expansions, as well as from differentiation hierarchies existent in the tumor, such as that established by cancer stem cells (cscs) and non-cscs. these differentiation hierarchies may arise due ... | 2015 | 25482627 |
| eph receptor and ephrin function in breast, gut, and skin epithelia. | epithelial cells are tightly coupled together through specialized intercellular junctions, including adherens junctions, desmosomes, tight junctions, and gap junctions. a growing body of evidence suggests epithelial cells also directly exchange information at cell-cell contacts via the eph family of receptor tyrosine kinases and their membrane-associated ephrin ligands. ligand-dependent and -independent signaling via eph receptors as well as reverse signaling through ephrins impact epithelial ti ... | 2014 | 25482622 |
| modulation of tumor fatty acids, through overexpression or loss of thyroid hormone responsive protein spot 14 is associated with altered growth and metastasis. | spot14 (s14), encoded by the thrsp gene, regulates de novo fatty acid synthesis in the liver, adipose, and lactating mammary gland. we recently showed that s14 stimulated fatty acid synthase (fasn) activity in vitro, and increased the synthesis of fatty acids in mammary epithelial cells in vivo. elevated de novo fatty acid synthesis is a distinguishing feature of many solid tumors compared with adjacent normal tissue. this characteristic is thought to be acquired during tumor progression, as rap ... | 2014 | 25472762 |
| inactivation of rarβ inhibits wnt1-induced mammary tumorigenesis by suppressing epithelial-mesenchymal transitions. | retinoic acid receptor β (rarβ) has been proposed to act as a tumor suppressor in breast cancer. in contrast, recent data have shown that rarβ promotes erbb2-induced mammary gland tumorigenesis through remodeling of the stromal compartment and activation of cancer-associated fibroblasts. however, it is currently unknown whether rarβ oncogenic activity is specific to erbb2-induced tumors, or whether it influences the initiation and progression of other breast cancer subtypes. accordingly, we set ... | 2014 | 25422594 |
| structural basis of genomic rna (grna) dimerization and packaging determinants of mouse mammary tumor virus (mmtv). | one of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral grna in the form of a non-covalent rna dimer by the assembling virions. it is becoming increasingly clear that the process of dimerization is closely linked with grna packaging, and in some retroviruses, the latter depends on the former. earlier mutational analysis of the 5' end of the mmtv genome indicated that mmtv grna packaging determinants comprise sequences both within the 5' u ... | 2014 | 25394412 |
| intravital imaging reveals distinct responses of depleting dynamic tumor-associated macrophage and dendritic cell subpopulations. | tumor-infiltrating inflammatory cells comprise a major part of the stromal microenvironment and support cancer progression by multiple mechanisms. high numbers of tumor myeloid cells correlate with poor prognosis in breast cancer and are coupled with the angiogenic switch and malignant progression. however, the specific roles and regulation of heterogeneous tumor myeloid populations are incompletely understood. csf-1 is a major myeloid cell mitogen, and signaling through its receptor csf-1r is a ... | 2014 | 25385645 |
| fli1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression. | ets factors have been shown to be dysregulated in breast cancer. ets factors control the expression of genes involved in many biological processes, such as cellular proliferation, differentiation, and apoptosis. fli1 is an ets protein aberrantly expressed in retrovirus-induced hematological tumors, but limited attention has been directed towards elucidating the role of fli1 in epithelial-derived cancers. using data mining, we show that loss of fli1 expression is associated with shorter survival ... | 2014 | 25379017 |
| dietary vitamin a regulates wingless-related mmtv integration site signaling to alter the hair cycle. | alopecia areata (aa) is an autoimmune hair loss disease caused by a cell-mediated immune attack of the lower portion of the cycling hair follicle. feeding mice 3-7 times the recommended level of dietary vitamin a accelerated the progression of aa in the graft-induced c3h/hej mouse model of aa. in this study, we also found that dietary vitamin a, in a dose dependent manner, activated the hair follicle stem cells (scs) to induce the development and growth phase of the hair cycle (anagen), which ma ... | 2015 | 25361771 |
| no evidence of mammary tumor virus env gene-like sequences among iranian women with breast cancer. | the mouse mammary tumor virus (mmtv) is the well-established etiological agent of mammary tumors in mice. a series of studies have implicated that a human murine mammary tumor virus-like virus occurs in human breast cancer, but it is unclear whether it has any causal role. | 2014 | 25323846 |
| impact of combination antiretroviral therapy in the nod.c3c4 mouse model of autoimmune biliary disease. | the nod.c3c4 mouse model develops autoimmune biliary disease characterized by spontaneous granulomatous cholangitis, antimitochondrial antibodies and liver failure. this model for primary biliary cirrhosis (pbc) has evidence of biliary infection with mouse mammary tumour virus (mmtv), suggesting that the virus may have a role in cholangitis development and progression of liver disease in this mouse model. we tested the hypothesis that mmtv infection is associated with cholangitis in the nod.c3c4 ... | 2015 | 25302564 |
| new perspectives on β-catenin control of cell fate and proliferation in colon cancer. | colorectal cancer is a major health problem worldwide. aberrant activation of the wingless-type mouse mammary tumor virus integration site family(wnt)/β-catenin signaling pathway is the most common and initial alteration in sporadic colorectal tumors. numerous experimental studies have indicated that β-catenin is a key regulator of colorectal cancer. indeed, β-catenin activity was shown to designate colon cancer stem cells (csc) and is, therefore, an attractive target for new therapeutic agents. ... | 2014 | 25193262 |
| [generation and comparison of two genetically engineered mouse models of erbb2/neu positive-pten deficient breast cancer]. | to generate two genetically engineered mouse models of erbb2/neu positive-pten deficient breast cancer and to compare their biological properties. | 2014 | 25187457 |
| human mammary tumor virus (hmtv) sequences in human milk. | retroviral sequences 90-95% homologous to the mouse mammary tumor virus (mmtv) were present in 38% of the breast cancers studied from american women and were not detectable in non-tumor breast tissue from the same patient. the entire proviral structure was described and viral particles were isolated from primary cultures of human breast cancer. this virus was designated as human mammary tumor virus (hmtv). hormone response elements present in the hmtv long-terminal-repeat (ltr) suggest a mechani ... | 2014 | 25120582 |
| the distribution of insertionally polymorphic endogenous retroviruses in breast cancer patients and cancer-free controls. | integration of retroviral dna into a germ cell can result in a provirus that is transmitted vertically to the host's offspring. in humans, such endogenous retroviruses (hervs) comprise >8% of the genome. the herv-k(hml-2) proviruses consist of ~90 elements related to mouse mammary tumor virus, which causes breast cancer in mice. a subset of herv-k(hml-2) proviruses has some or all genes intact, and even encodes functional proteins, though a replication competent copy has yet to be observed. more ... | 2014 | 25112280 |
| estrogen receptor inhibits mineralocorticoid receptor transcriptional regulatory function. | the steroid hormone aldosterone (aldo) contributes to cardiovascular disease in animal models and in humans. aldo activates the mineralocorticoid receptor (mr), a hormone-activated transcription factor, and indeed, pharmacological mr inhibition improves cardiovascular outcomes. because the incidence of cardiovascular disease is lower in premenopausal women, we hypothesized that estrogen (e2) signaling through the estrogen receptor (er) may protect the vasculature by inhibiting the detrimental ef ... | 2014 | 25051445 |
| wnt16b from ovarian fibroblasts induces differentiation of regulatory t cells through β-catenin signal in dendritic cells. | treatment for cancer can induce a series of secreted factors into the tumor microenvironment, which can affect cancer progression. wingless-type mmtv (mouse mammary tumor virus) integration site 16b (wnt16b) is a new member of the wnt family and has been reported to play growth-related roles in previous studies. in this study, we found wnt16b could be expressed and secreted into the microenvironment by human ovarian fibroblasts after dna damage-associated treatment, including chemotherapy drugs ... | 2014 | 25050785 |
| deletion of cd151 reduces mammary tumorigenesis in the mmtv/pymt mouse model. | tetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling. cd151 is part of the tetraspanin family and it forms tight complexes with β1 and β4 integrins, both of which have been shown to be required for tumorigenesis and/or metastasis in transgenic mouse models of breast cancer. high levels of ... | 2014 | 25012362 |
| challenging role of wnt5a and its signaling pathway in cancer metastasis (review). | wnt5a is a noncanonical signaling member of the wingless-related/mouse mammary tumor virus integration family, which is involved in a wide range of cellular processes, particularly in cancer development and metastasis. accumulating evidence indicates that wnt5a exhibits paradoxical effects in various types of cancer metastasis. therefore, the wnt5a signaling cascade in cancer metastasis appears to be complex and may depend on binding receptors, downstream effectors, exogenous inhibitors and tumo ... | 2014 | 24944588 |
| mouse mammary tumor virus-like virus infection and the risk of human breast cancer: a meta-analysis. | despite a large number of molecular epidemiological studies, the association of mouse mammary tumor virus-like virus (mmtv-lv) infection with the risk of human breast cancer remains inconclusive mainly due to the heterogeneity in populations involved. we performed a systematic search of multiple bibliographic databases, up to october 2013, to identify all studies on detection of mmtv-lv dna in human breast cancer using polymerase chain reaction (pcr) and conducted the first comprehensive meta-an ... | 2014 | 24936218 |
| the e2f transcription factors regulate tumor development and metastasis in a mouse model of metastatic breast cancer. | while the e2f transcription factors (e2fs) have a clearly defined role in cell cycle control, recent work has uncovered new functions. using genomic signature methods, we predicted a role for the activator e2f transcription factors in the mouse mammary tumor virus (mmtv)-polyomavirus middle t oncoprotein (pymt) mouse model of metastatic breast cancer. to genetically test the hypothesis that the e2fs function to regulate tumor development and metastasis, we interbred mmtv-pymt mice with e2f1, e2f ... | 2014 | 24934442 |
| the wnt signaling antagonist dickkopf-1 directs lineage commitment and promotes survival of the preimplantation embryo. | successful embryonic development is dependent on factors secreted by the reproductive tract. dickkopf-1 (dkk1), an antagonist of the wingless-related mouse mammary tumor virus (wnt) signaling pathway, is one endometrial secretory protein potentially involved in maternal-embryo communication. the purpose of this study was to investigate the roles of dkk1 in embryo cell fate decisions and competence to establish pregnancy. using in vitro-produced bovine embryos, we demonstrate that exposure of emb ... | 2014 | 24858280 |
| activation of noncanonical wnt signaling through wnt5a in visceral adipose tissue of obese subjects is related to inflammation. | wingless-type mouse mammary tumor virus integration site family (wnt)-5a is a glycoprotein involved in the regulation of the inflammatory response by activating the noncanonical wnt signaling pathway. secreted frizzled-related protein (sfrp)-5 acts as a decoy receptor that binds and sequesters wnt5a, preventing activation of frizzled receptors and attenuating the noncanonical wnt signaling. | 2014 | 24840810 |
| detection and identification of mouse mammary tumor virus-like dna sequences in blood and breast tissues of breast cancer patients. | mouse mammary tumor virus (mmtv) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. the hypothesis that a retrovirus homologous to mmtv is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. therefore, the detection of mmtv-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. to detect the prevalence of mmtv in pak ... | 2014 | 24839004 |
| maternal metabolic perturbations elicited by high-fat diet promote wnt-1-induced mammary tumor risk in adult female offspring via long-term effects on mammary and systemic phenotypes. | many adult chronic diseases are thought to be influenced during early life by maternal nutrition; however, the underlying mechanisms remain largely unknown. obesity-related diseases may be due partly to high fat consumption. herein, we evaluated mammary tumor risk in female mouse mammary tumor virus-wnt-1 transgenic (tg) offspring exposed to high-fat diet (hfd) or control diet (cd) (45% and 17% kcal from fat, respectively) during gestation and lactation, with cd provided to progeny at weaning. i ... | 2014 | 24832086 |
| conditionally reprogrammed normal and transformed mouse mammary epithelial cells display a progenitor-cell-like phenotype. | mammary epithelial (me) cells cultured under conventional conditions senesce after several passages. here, we demonstrate that mouse me cells isolated from normal mammary glands or from mouse mammary tumor virus (mmtv)-neu-induced mammary tumors, can be cultured indefinitely as conditionally reprogrammed cells (crcs) on irradiated fibroblasts in the presence of the rho kinase inhibitor y-27632. cell surface progenitor-associated markers are rapidly induced in normal mouse me-crcs relative to me ... | 2014 | 24831228 |
| mammary cancer chemoprevention by withaferin a is accompanied by in vivo suppression of self-renewal of cancer stem cells. | current dogma favors elimination of therapy-resistant cancer stem cells for chemoprevention of breast cancer. we showed recently that mammary cancer development in a transgenic mouse model (mouse mammary tumor virus-neu; mmtv-neu) was inhibited significantly upon treatment with withaferin a (wa), a steroidal lactone derived from a medicinal plant. herein, we demonstrate that the mammary cancer prevention by wa is accompanied by in vivo suppression of breast cancer stem cells (bcsc). in vitro mam ... | 2014 | 24824039 |
| ew-7197, a novel alk-5 kinase inhibitor, potently inhibits breast to lung metastasis. | advanced tumors produce an excessive amount of transforming growth factor β (tgfβ), which promotes tumor progression at late stages of malignancy. the purpose of this study was to develop anti-tgfβ therapeutics for cancer. we synthesized a novel small-molecule tgfβ receptor i kinase (activin receptor-like kinase 5) inhibitor termed n-[[4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1h-imidazol-2-yl]methyl]-2-fluoroaniline (ew-7197), and we investigated its potential antimetastat ... | 2014 | 24817629 |
| secreted phosphoprotein 1 is a determinant of lung function development in mice. | secreted phosphoprotein 1 (spp1) is located within quantitative trait loci associated with lung function that was previously identified by contrasting c3h/hej and jf1/msf mouse strains that have extremely divergent lung function. jf1/msf mice with diminished lung function had reduced lung spp1 transcript and protein during the peak stage of alveologenesis (postnatal day [p]14-p28) as compared with c3h/hej mice. in addition to a previously identified genetic variant that altered runt-related tran ... | 2014 | 24816281 |
| protein kinase c beta in the tumor microenvironment promotes mammary tumorigenesis. | protein kinase c beta (pkcβ) expression in breast cancer is associated with a more aggressive tumor phenotype, yet the mechanism for how pkcβ is pro-tumorigenic in this disease is still unclear. interestingly, while it is known that pkcβ mediates angiogenesis, immunity, fibroblast function and adipogenesis, all components of the mammary tumor microenvironment (tme), no study to date has investigated whether stromal pkcβ is functionally relevant in breast cancer. herein, we evaluate mouse mammary ... | 2014 | 24795864 |
| overexpression of notch-regulated ankyrin repeat protein is associated with breast cancer cell proliferation. | notch-regulated ankyrin repeat protein (nrarp) has been implicated in crosstalk between notch and wingless-type mouse mammary tumor virus integration site (wnt) signals during development. our study aimed to clarify its role in breast cancer cells. | 2014 | 24778018 |