Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
|---|
| hypoxia modulation and radiosensitization by the novel dual egfr and vegfr inhibitor aee788 in spontaneous and related allograft tumor models. | concomitant inhibition of erbb1/2- and vegf receptor-signaling synergizes when used in combination with dna-damaging agents. here, we investigated for the first time the combined treatment modality of the novel dual specific receptor tyrosine kinase inhibitor aee788 with ionizing radiation and analyzed treatment-induced end points in situ as indicators for a potential sensitizing mechanism. furthermore, we assessed tumor hypoxia in response to different antiangiogenic and antiproliferative treat ... | 2007 | 17876047 |
| a new rexinoid, nrx194204, prevents carcinogenesis in both the lung and mammary gland. | we evaluated the anti-inflammatory and growth-inhibitory properties of the novel rexinoid nrx194204 (4204) in vitro and then tested its ability to prevent and/or treat experimental lung and estrogen receptor (er)-negative breast cancer in vivo. | 2007 | 17947492 |
| expression of truncated int6/eif3e in mammary alveolar epithelium leads to persistent hyperplasia and tumorigenesis. | int6 has been shown to be an interactive participant with the protein translation initiation complex eif3, the cop9 signalosome and the regulatory lid of the 26s proteasome. insertion of mouse mammary tumor virus into the int6 locus creates a c-terminally truncated form of the protein. expression of the truncated form of int6 (int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. in addition, decreased expression of int6/eif3e is observed i ... | 2007 | 17626637 |
| an egr2/cited1 transcription factor complex and the 14-3-3sigma tumor suppressor are involved in regulating erbb2 expression in a transgenic-mouse model of human breast cancer. | amplification and elevated expression of the erbb2 receptor tyrosine kinase occurs in 20% of human breast cancers and is associated with a poor prognosis. we have previously demonstrated that mammary tissue-specific expression of activated erbb2 under the control of its endogenous promoter results in mammary tumor formation. tumor development was associated with amplification and overexpression of erbb2 at both the transcript and protein levels. here we demonstrate that the egr2/krox20 transcrip ... | 2007 | 17938205 |
| a novel point mutation in helix 11 of the ligand-binding domain of the human glucocorticoid receptor gene causing generalized glucocorticoid resistance. | generalized glucocorticoid resistance is a rare condition characterized by partial, end-organ insensitivity to glucocorticoids, compensatory elevations in adrenocorticotropic hormone and cortisol secretion, and increased production of adrenal steroids with androgenic and/or mineralocorticoid activity. we have identified a new case of glucocorticoid resistance caused by a novel mutation of the human glucocorticoid receptor (hgr) gene and studied the molecular mechanisms through which the mutant r ... | 2007 | 17635946 |
| jaagsiekte sheep retrovirus is not detected in human lung adenocarcinomas expressing antigens related to the gag polyprotein of betaretroviruses. | a proportion of human lung adenocarcinomas (hlacs) express an antigen related to the major capsid protein (ca) of jaagsiekte sheep retrovirus (jsrv), a betaretrovirus that causes a transmissible lung cancer in sheep. in this study, we have investigated whether jsrv or related betaretroviruses are expressed in hlacs. results obtained indicate that jsrv is not associated with human lung adenocarcinomas. however, a proportion of hlacs reacted positively in immunohistochemistry with antibodies speci ... | 2007 | 17889995 |
| the int6 cancer gene and mek signaling pathways converge during zebrafish development. | int-6 (integration site 6) was identified as an oncogene in a screen of tumorigenic mouse mammary tumor virus (mmtv) insertions. int6 expression is altered in human cancers, but the precise role of disrupted int6 in tumorigenesis remains unclear, and an animal model to study int-6 physiological function has been lacking. | 2007 | 17895999 |
| rapid spread of mouse mammary tumor virus in cultured human breast cells. | the role of mouse mammary tumor virus (mmtv) as a causative agent in human breast carcinogenesis has recently been the subject of renewed interest. the proposed model is based on the detection of mmtv sequences in human breast cancer but not in healthy breast tissue. one of the main drawbacks to this model, however, was that until now human cells had not been demonstrated to sustain productive mmtv infection. | 2007 | 17931409 |
| a mouse model for luminal epithelial like er positive subtype of human breast cancer. | generation of novel spontaneous er positive mammary tumor animal model from heterozygous nih nude mice. | 2007 | 17880731 |
| iron accumulation in mammary tumor suggests a tug of war between tumor and host for the microelement. | iron is indispensable for the metabolism and proliferation of both normal and malignant cells. recycling from senescent erythrocytes in the liver and spleen is critical for iron supply to all tissues. in the liver and spleen from mmtv-neu (erbb-2) mice bearing a mammary carcinoma, we noticed the scarcity of hemosiderin pigment and its abundance in the stroma of the tumor. thus iron (iii) was investigated with the perls' reaction in tissues from normal and mmtv-neu mice. with respect to normal an ... | 2007 | 17970045 |
| aly is a common coactivator of runx1 and c-myb on the type b leukemogenic virus enhancer. | type b leukemogenic virus (tblv), a mouse mammary tumor virus (mmtv) variant, often induces t-cell leukemias and lymphomas by c-myc activation following viral dna integration. transfection assays using a c-myc reporter plasmid indicated that the tblv long terminal repeat (ltr) enhancer is necessary for t-cell-specific increases in basal reporter activity. the sequence requirements for this effect were studied using mutations of the 62-bp enhancer region in an mmtv ltr reporter vector. deletion o ... | 2007 | 17229714 |
| mouse mammary tumour-like virus gene sequences and specific breast cancer morphology. | 2007 | 17158634 | |
| rank overexpression in transgenic mice with mouse mammary tumor virus promoter-controlled rank increases proliferation and impairs alveolar differentiation in the mammary epithelia and disrupts lumen formation in cultured epithelial acini. | rank and rankl, the key regulators of osteoclast differentiation and activation, also play an important role in the control of proliferation and differentiation of mammary epithelial cells during pregnancy. here, we show that rank protein expression is strictly regulated in a spatial and temporal manner during mammary gland development. rank overexpression under the control of the mouse mammary tumor virus (mmtv) promoter in a transgenic mouse model results in increased mammary epithelial cell p ... | 2007 | 17145767 |
| mechanism of histone h1-stimulated glucocorticoid receptor dna binding in vivo. | xenopus oocytes lack somatic linker histone h1 but contain an oocyte-specific variant, b4. the glucocorticoid receptor (gr) inducible mouse mammary tumor virus (mmtv) promoter was reconstituted in xenopus oocytes to address the effects of histone h1. the expression of xenopus h1o [corrected] (h1) via cytoplasmic mrna injection resulted in h1 incorporation into in vivo assembled chromatin based on (i) the appearance of a chromatosome stop, (ii) the increased nucleosome repeat length (nrl), and (i ... | 2007 | 17210632 |
| neu-mediated phosphorylation of protein tyrosine phosphatase epsilon is critical for activation of src in mammary tumor cells. | the receptor-type protein tyrosine phosphatase epsilon (rptpepsilon) activates c-src in mammary tumor cells induced in vivo by neu. tumor cells lacking rptpepsilon exhibit reduced c-src activity, appear less transformed morphologically and proliferate slower in vitro and in vivo. expression of src rescues most of these phenotypes, indicating that c-src activity is important for maintaining the transformed phenotype. however, the molecular mechanisms that control activation of c-src by rptpepsilo ... | 2007 | 17486066 |
| recirculating cd4 memory t cells mount rapid secondary responses without major contributions from follicular cd4 effectors and b cells. | for weeks after primary immunization with thymus-dependent antigens the responding lymph nodes contain effector cd4 t cells in t zones and germinal centers as well as recirculating memory t cells. conversely, remote nodes, not exposed to antigen, only receive recirculating memory cells. we assessed whether lymph nodes with follicular effector cd4 t cells in addition to recirculating memory cd4 t cells mount a more rapid secondary response than nodes that only contain recirculating memory cells. ... | 2007 | 17506034 |
| androgen receptor co-activator hic-5/ara55 as a molecular regulator of androgen sensitivity in dermal papilla cells of human hair follicles. | androgen site-specifically affects human hair growth after puberty through androgen receptors in the dermal papilla, which transactivate target genes acting in conjunction with co-activators. to examine the regulation of androgen sensitivity in hair follicles, we focused on androgen receptor co-activator hic-5/ara55. its interaction with transfected androgen receptor in beard dermal papilla cells was confirmed with mammalian two-hybrid assays. the semiquantitative reverse transcriptase-polymeras ... | 2007 | 17508020 |
| female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor beta signaling in salivary glands. | transforming growth factor beta (tgfbeta) plays a key role in the onset and resolution of autoimmune diseases and chronic inflammation. the aim of this study was to delineate the precise function of tgfbeta signaling in salivary gland inflammation. | 2007 | 17530708 |
| independent and complementary methods for large-scale structural analysis of mammalian chromatin. | the fundamental building block of chromatin, the nucleosome, occupies 150 bp of dna in a spaced arrangement that is a primary determinant in regulation of the genome. the nucleosomal organization of some regions of the human genome has been described, but mapping of these regions has been limited to a few kilobases. we have explored two independent and complementary methods for the high-throughput analysis of mammalian chromatin structure. through adaptations to a protocol used to map yeast chro ... | 2007 | 17568008 |
| secretion of pleiotrophin stimulates breast cancer progression through remodeling of the tumor microenvironment. | pleiotrophin (ptn, ptn) is an 18-kda secretory cytokine expressed in many breast cancers; however, the significance of ptn expression in breast cancer has not been established. we have now tested three models to determine the role of inappropriate expression of ptn in breast cancer. mouse mammary tumor virus (mmtv) promoter-driven ptn expressed in mmtv-polyoma virus middle t antigen (pymt)-ptn mouse breast cancers was first shown to induce rapid growth of morphologically identified foci of "scir ... | 2007 | 17578909 |
| subcellular localization modulates activation function 1 domain phosphorylation in the androgen receptor. | although the steady-state distribution of the androgen receptor (ar) is predominantly nuclear in androgen-treated cells, androgen-bound ar shuttles between the nucleus and the cytoplasm. in the present study we have addressed how nucleocytoplasmic shuttling contributes to the regulation of ar. nuclear transport signal fusions were used to force ar localization to the nucleus or cytoplasm of prostate cancer cells, and the effect of localization on shuttling, transcription, androgen binding, and p ... | 2007 | 17579212 |
| activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized lbetat2 gonadotrope cell line. | fsh is produced by the pituitary gonadotrope to regulate gametogenesis. production of the beta-subunit of fsh is the rate-limiting step in fsh synthesis, and a number of peptide and steroid hormones within the reproductive axis have been found to regulate transcription of the fsh beta-subunit gene. although both activin and glucocorticoids are notable regulators of fshbeta by themselves, we find that cotreatment results in a synergistic interaction on the mouse fshbeta promoter at the level of t ... | 2007 | 17082263 |
| proteasome activity modulates chromatin modifications and rna polymerase ii phosphorylation to enhance glucocorticoid receptor-mediated transcription. | the 26s proteasome modulates steroid hormone receptor-dependent gene transcription at least in part by regulating turnover and recycling of receptor/transcriptional dna complexes, thereby ensuring continued hormone response. for the glucocorticoid receptor (gr), inhibition of proteasome-mediated proteolysis or rna interference-mediated depletion of specific proteasome subunits results in an increase in gene expression. to facilitate transcription, proteasome inhibition alters at least two featur ... | 2007 | 17438138 |
| mmtv insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer. | we performed a high-throughput retroviral insertional mutagenesis screen in mouse mammary tumor virus (mmtv)-induced mammary tumors and identified 33 common insertion sites, of which 17 genes were previously not known to be associated with mammary cancer and 13 had not previously been linked to cancer in general. although members of the wnt and fibroblast growth factors (fgf) families were frequently tagged, our exhaustive screening for mmtv insertion sites uncovered a new repertoire of candidat ... | 2007 | 17468756 |
| effects of brca1 transgene expression on murine mammary gland development and mutagen-induced mammary neoplasia. | to characterize the role of brca1 in mammary gland development and tumor suppression, a transgenic mouse model of brca1 overexpression was developed. using the mouse mammary tumor virus (mmtv) promoter/enhancer, transgenic mice expressing human brca1 or select mutant controls were generated. transgenic animals examined during adolescence were shown to express the human transgene in their mammary glands. the mammary glands of 13-week-old virgin homozygous mmtv-brca1 mice presented the morphology ... | 2007 | 17505536 |
| endothelial akt signaling is rate-limiting for rapamycin inhibition of mouse mammary tumor progression. | chronic activation of akt signaling in the endothelium recapitulates the salient features of a tumor vasculature and can be inhibited by rapamycin, an inhibitor of mammalian target of rapamycin. this led to the hypothesis that the antitumor efficacy of rapamycin may be partially dependent on its ability to inhibit endothelial akt signaling, making rapamycin an antiangiogenic agent and endothelial akt pathway inhibitor. dose-response studies with rapamycin showed that primary human endothelial ce ... | 2007 | 17545582 |
| critical role of dendritic cells in mouse mammary tumor virus in vivo infection. | mouse mammary tumor virus (mmtv) is a milk-transmitted betaretrovirus that causes mammary tumors in mice. although mammary epithelial cells are the ultimate targets of mmtv, the virus utilizes components of the host immune system to establish infection. previous studies indicated that dendritic cells play a role in mmtv infection. here we show that dendritic cells are the first cells to be infected by mmtv in vivo and that they are capable of producing infectious virus that can be transmitted to ... | 2007 | 17267484 |
| constitutive activation of smoothened (smo) in mammary glands of transgenic mice leads to increased proliferation, altered differentiation and ductal dysplasia. | the hedgehog signaling network regulates pattern formation, proliferation, cell fate and stem/progenitor cell self-renewal in many organs. altered hedgehog signaling is implicated in 20-25% of all cancers, including breast cancer. we demonstrated previously that heterozygous disruption of the gene encoding the patched-1 (ptch1) hedgehog receptor, a negative regulator of smoothened (smo) in the absence of ligand, led to mammary ductal dysplasia in virgin mice. we now show that expression of activ ... | 2007 | 17287253 |
| human int6 interacts with mcm7 and regulates its stability during s phase of the cell cycle. | the mouse int6 gene is a frequent integration site of the mouse mammary tumor virus and int6 silencing by rna interference in hela cells causes an increased number of cells in the g2/m phases of the cell cycle, along with mitotic defects. in this report, we investigated the functional significance of the interaction between int6 and mcm7, which was observed in a two-hybrid screen performed with int6 as bait. it was found that proteasome inhibition strengthens interaction between both proteins an ... | 2007 | 17310990 |
| the soluble wnt receptor frizzled8crd-hfc inhibits the growth of teratocarcinomas in vivo. | wnt signaling is important for normal cell proliferation and differentiation, and mutations in pathway components are associated with human cancers. recent studies suggest that altered wnt ligand/receptor interactions might also contribute to human tumorigenesis. therefore, agents that antagonize wnt signaling at the extracellular level would be attractive therapeutics for these cancers. we have generated a soluble wnt receptor comprising the frizzled8 cysteine-rich domain (crd) fused to the hum ... | 2007 | 17545618 |
| protein-tyrosine phosphatase 1b is required for her2/neu-induced breast cancer. | the protein-tyrosine phosphatase 1b (ptp1b; ptpn1) is an important regulator of mammalian metabolism and also helps control signaling by growth factors, cytokines, and extracellular matrix. gene knockout studies in mice established ptp1b as a key negative regulator of the insulin and leptin receptors. experiments using ptp1b(-/-) fibroblast lines, dominant-negative mutants, or small interfering rnas indicate that ptp1b contributes to dephosphorylation of the epidermal growth factor receptor and ... | 2007 | 17347513 |
| fhit expression protects against her2-driven breast tumor development: unraveling the molecular interconnections. | the tumor suppressor gene fhit is inactivated by genetic and epigenetic changes, i.e., loss of heterozygosity or promoter hypermethylation, in common human cancers. we recently showed that fhit protein levels can be regulated by fhit proteasome degradation mediated by egf-dependent activation of egfr family members, including her2, whose overexpression is linked to poor prognosis in breast cancer. analysis of a series of 384 human primary breast carcinomas revealed low/absent fhit protein levels ... | 2007 | 17374991 |
| sumoylation and proteasomal activity determine the transactivation properties of the mineralocorticoid receptor. | mr is a hormone-activated transcription factor that carries a strong synergy inhibitory function at its n-terminus. using this region as bait in a yeast two-hybrid screening, we isolated major components of the sumoylation pathway, including the sumo-1-conjugating enzyme ubc9, and sumo-1 itself. we found that mr interacts with both, ubc9 and sumo-1 in mammalian cells, and that the receptor is sumoylated at four acceptor sites which are clustered within its af-1 domain. we observed that mr can be ... | 2007 | 17314004 |
| an active nuclear retention signal in the glucocorticoid receptor functions as a strong inducer of transcriptional activation. | the glucocorticoid receptor (gr) cycles between a naive chaperone-complexed form in the cytoplasm and a transcriptionally active steroid-bound nuclear form. nuclear import of gr occurs rapidly and is mediated through the importin alpha/beta karyopherin import pathway. by contrast, nuclear export of gr occurs only slowly under most conditions, despite a dependence on active signaling. in this study we have defined a nuclear retention signal (nrs) in the hinge region of gr that actively opposes th ... | 2007 | 17314103 |
| promotion of breast cancer by beta-hexachlorocyclohexane in mcf10at1 cells and mmtv-neu mice. | exposure to beta-hexachlorocyclohexane (beta-hch), a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. previous studies in our laboratory have demonstrated the ability of beta-hch to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-neu (= erbb2 or her-2) expression and kinase activation in both the bg-1 and mcf-7 cell lines. in addition, lo ... | 2007 | 17640349 |
| hyperproduction of hyaluronan in neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment: possible involvement of versican/pg-m. | elevated concentrations of hyaluronan are often associated with human breast cancer malignancy. here, we investigated the roles of hyaluronan in carcinogenesis and cancer progression using the mouse mammary tumor virus (mmtv)-neu transgenic model of spontaneous breast cancer. conditional transgenic mice that express murine hyaluronan synthase 2 (has2) by cre-mediated recombination were generated and crossed with the mmtv-neu mice. in expressing cre recombinase under the control of the mmtv promo ... | 2007 | 17322391 |
| incorporation of high levels of chimeric human immunodeficiency virus envelope glycoproteins into virus-like particles. | the human immunodeficiency virus (hiv) envelope (env) protein is incorporated into hiv virions or virus-like particles (vlps) at very low levels compared to the glycoproteins of most other enveloped viruses. to test factors that influence hiv env particle incorporation, we generated a series of chimeric gene constructs in which the coding sequences for the signal peptide (sp), transmembrane (tm), and cytoplasmic tail (ct) domains of hiv-1 env were replaced with those of other viral or cellular p ... | 2007 | 17670815 |
| tumors initiated by constitutive cdk2 activation exhibit transforming growth factor beta resistance and acquire paracrine mitogenic stimulation during progression. | cyclin d1/cyclin-dependent kinase 2 (cdk2) complexes are present at high frequency in human breast cancer cell lines, but the significance of this observation is unknown. this report shows that expression of a cyclin d1-cdk2 fusion protein under the control of the mouse mammary tumor virus (mmtv) promoter results in mammary gland hyperplasia and fibrosis, and mammary tumors. cell lines isolated from mmtv-cyclin d1-cdk2 (mmtv-d1k2) tumors exhibit rb and p130 hyperphosphorylation and up-regulation ... | 2007 | 17409420 |
| inhibition of tgf-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. | we investigated whether tgf-beta induced by anticancer therapies accelerates tumor progression. using the mmtv/pyvmt transgenic model of metastatic breast cancer, we show that administration of ionizing radiation or doxorubicin caused increased circulating levels of tgf-beta1 as well as increased circulating tumor cells and lung metastases. these effects were abrogated by administration of a neutralizing pan-tgf-beta antibody. circulating polyomavirus middle t antigen-expressing tumor cells did ... | 2007 | 17415413 |
| mouse mammary tumor biology: a short history. | 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 m ... | 2007 | 17433908 |
| properties of nucleosomes in acetylated mouse mammary tumor virus versus 5s arrays. | acetylation is one of the most abundant histone modifications found in nucleosomes. although such modifications are thought to function mainly in recognition, acetylation is known to produce nucleosome structural alterations. these could be of functional significance in vivo. here, the basic features of mouse mammary tumor virus (mmtv) promoter nucleosomal arrays reconstituted with highly acetylated histones prepared from butyrate-treated hela cells are characterized by atomic force microscopy. ... | 2007 | 17444617 |
| search for dna of exogenous mouse mammary tumor virus-related virus in human breast cancer samples. | earlier reports of a human exogenous retrovirus (hmtv) related closely to mouse mammary tumor virus (mmtv) led us to search for these viral sequences in breast cancer tissues and normal tissues. a real-time pcr was developed based on mmtv and published hmtv envelope sequences. the real-time pcr method can detect one to ten copies of mmtv target dna. tissue samples were collected prospectively from 18 breast cancer patients and 11 non-malignant control cases, as well as peripheral blood leukocyte ... | 2007 | 17485542 |
| mammalian tumor suppressor int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pvhl-independent regulation. | the hypoxia-inducible factors hif-1 alpha and hif-2 alpha are structurally similar as regards their dna-binding and dimerization domains, but differ in their transactivation domains and, as is shown by experiments using hif-1 alpha(-/-) and hif-2 alpha(-/-) mice, in their functions. this implies that hif-1 alpha and hif-2 alpha may have unique target genes. to address this discrepancy and identify hif-2 alpha-specific target genes, we performed yeast two-hybrid analysis and identified the tumor ... | 2007 | 17324924 |
| effects of neurosteroids on glucocorticoid receptor-mediated gene transcription in lmcat cells--a possible interaction with psychotropic drugs. | aberrant activity of hypothalamic-pituitary-adrenal (hpa) axis is often observed in psychiatric disorders and both antidepressant and antipsychotic drugs are known to ameliorate some deleterious effects of glucocorticoids on brain function. some neurosteroids possess antidepressant and neuroleptic-like properties and attenuate the stress-activated hpa axis activity. however, intracellular mechanism of neurosteroid interaction with glucocorticoids has not been elucidated. we evaluated effects of ... | 2007 | 16581232 |
| kit and pdgfr-alpha activities are necessary for notch4/int3-induced tumorigenesis. | transgenic mice overexpressing notch4 intracellular domain (int3) under the control of the whey acidic protein (wap) or mouse mammary tumor virus-long terminal repeat promoters, develop mammary tumors. microarray analysis of these tumors revealed high levels of c-kit expression. gleevec is a tyrosine kinase inhibitor that targets c-kit, platelet-derived growth factor receptors (pdgfrs) and c-abl. this led us to speculate that tyrosine kinase receptor activity might be a driving force in the deve ... | 2007 | 16878155 |
| apobec3 inhibits mouse mammary tumour virus replication in vivo. | genomes of all mammals encode apobec3 genes, which are thought to have a function in intrinsic cellular immunity to several viruses including human immunodeficiency virus type 1 (hiv-1). apobec3 (a3) proteins are packaged into virions and inhibit retroviral replication in newly infected cells, at least in part by deaminating cytidines on the negative strand dna intermediates. however, the role of a3 in innate resistance to mouse retroviruses is not understood. here we show that a3 functions duri ... | 2007 | 17259974 |
| development of leiomyosarcoma of the uterus in mmtv-cr-1 transgenic mice. | overexpression of cripto-1 (cr-1) in fvb/n mice using the mmtv-ltr promoter results in increased mammary tumourigenesis in these female transgenic mice (mmtv-cr-1). here, we characterize uterine tumours that developed in 15/76 (19.7%) of mmtv-cr-1 female nulliparous or multiparous mice during 24 months of observation compared with 0/33 (0%) of fvb/n normal control mice observed during the same time period (p < 0.01). the uterine tumours collected from the mmtv-cr-1 mice were classified as leiomy ... | 2007 | 17072826 |
| immune response to mmtv infection. | mouse mammary tumor virus (mmtv) has developed a strategy of exploitation of the immune response. it infects dendritic cells and b cells and requires this infection to establish an efficient chronic infection. this allows transmission of infection to the mammary gland, production in milk and infection of the next generation via lactation. the elaborate strategy developed by mmtv utilizes several key elements of the normal immune response. starting with the infection and activation of dendritic c ... | 2007 | 17127406 |
| osmotic stress-dependent repression is mediated by histone h3 phosphorylation and chromatin structure. | histone h3 phosphorylation has been linked to various environmental stress responses and specific chromatin structure. the role of h3 phosphorylation in the osmotic stress response was investigated on the mouse mammary tumor virus (mmtv) promoter in different chromatin configurations. hormone-dependent transcription from the mmtv promoter is repressed by osmotic stress when the promoter is integrated and has a normal chromatin structure. however, when the mmtv promoter is transiently transfected ... | 2007 | 17158874 |
| chromatin-dependent cooperativity between site-specific transcription factors in vivo. | accessing binding sites in dna wrapped around histones in condensed chromatin is an obstacle that transcription factors must overcome to regulate gene expression. here we demonstrate cooperativity between two transcription factors, the glucocorticoid receptor (gr) and nuclear factor 1 (nf1) to bind the mouse mammary tumor virus promoter organized as regular chromatin in vivo. this cooperativity is not observed when the promoter is introduced transiently into cells. using rna interference to depl ... | 2007 | 17186943 |
| ligand-specific dynamics of the androgen receptor at its response element in living cells. | androgens have key roles in normal physiology and in male sexual differentiation as well as in pathological conditions such as prostate cancer. androgens act through the androgen receptor (ar), which is a ligand-modulated transcription factor. antiandrogens block ar function and are widely used in disease states, but little is known about their mechanism of action in vivo. here, we describe a rapid differential interaction of ar with target genomic sites in living cells in the presence of agonis ... | 2007 | 17189428 |
| prevention of mammary tumorigenesis by intermittent caloric restriction: does caloric intake during refeeding modulate the response? | chronic caloric restriction (ccr) prevents mammary tumorigenesis in rodents, but a protective effect for intermittent caloric restriction (icr) is less well documented. we recently reported that icr reduced mammary tumor (mt) incidence of mouse mammary tumor virus-transforming growth factor (mmtv-tgf)-alpha mice to a greater extent than did ccr. here, we repeated this protocol and obtained serum and tissue samples. ad libitum (al) mmtv-tgf-alpha mice were fed ain-93m diet. beginning at 10 weeks ... | 2007 | 17202587 |
| transcriptional cooperation between the transforming growth factor-beta and wnt pathways in mammary and intestinal tumorigenesis. | transforming growth factor-beta (tgf-beta) and wnt ligands function in numerous developmental processes, and alterations of both signaling pathways are associated with common pathologic conditions, including cancer. to obtain insight into the extent of interdependence of the two signaling cascades in regulating biological responses, we used an oligonucleotide microarray approach to identify wnt and tgf-beta target genes using normal murine mammary gland epithelial cells as a model. combination t ... | 2007 | 17210685 |
| bin1 ablation in mammary gland delays tissue remodeling and drives cancer progression. | genes that modify oncogenesis may influence dormancy versus progression in cancer, thereby affecting clinical outcomes. the bin1 gene encodes a nucleocytosolic adapter protein that interacts with and suppresses the cell transforming activity of myc. bin1 is often attenuated in breast cancer but its ability to negatively modify oncogenesis or progression in this context has not been gauged directly. in this study, we investigated the effects of mammary gland-specific deletion of bin1 on initiatio ... | 2007 | 17210688 |
| akt1 ablation inhibits, whereas akt2 ablation accelerates, the development of mammary adenocarcinomas in mouse mammary tumor virus (mmtv)-erbb2/neu and mmtv-polyoma middle t transgenic mice. | ample evidence to date links the phosphatidylinositol 3-kinase-regulated protein kinase akt with the induction and progression of human cancer, including breast cancer. however, there are three akt isoforms with limited information about their specificity during oncogenesis. this study addresses the role of the three isoforms in polyoma middle t (pymt) and erbb2/neu-driven mammary adenocarcinomas in mice. the effects of ablation of akt1, akt2, and akt3 on the induction and the biology of these t ... | 2007 | 17210696 |
| imaging tumors with an albumin-binding fab, a novel tumor-targeting agent. | association with albumin as a means to improve biodistribution and tumor deposition of a fab was investigated using ab.fab4d5, a bifunctional molecule derived from trastuzumab (herceptin) capable of binding albumin and tumor antigen her2 (erbb2) simultaneously. ab.fab4d5 was compared with trastuzumab and a trastuzumab-derived fab (fab4d5) for the ability to target tumors overexpressing her2 in mouse mammary tumor virus/her2 allograft models. biodistribution was monitored using intravital microsc ... | 2007 | 17210705 |
| inhibition of estrogen-induced mammary tumor formation in mmtv-aromatase transgenic mice by 4-chlorophenylacetate. | treatment of estrogen-sensitive breast cancer with selective estrogen selective modulators (serms) and, more recently, aromatase inhibitors has met with wide success. however, antagonism of estrogen receptor (er) activity in breast carcinomas by serms such as tamoxifen has been associated with increased risk of cancer in other tissue such as the endometrium. furthermore, current therapies using aromatase inhibitors have side effects on bone resulting in development of osteoporosis in some patien ... | 2007 | 17215075 |
| dynamic histone acetylation/deacetylation with progesterone receptor-mediated transcription. | histone acetylation is a highly dynamic posttranslational modification that plays an important role in gene expression. previous work showed that promoter histone deacetylation is accompanied by progesterone receptor (pr)-mediated activation of the mouse mammary tumor virus (mmtv) promoter. we investigated the role of this deacetylation and found that this histone deacetylation is not a singular event. in fact, histone acetylation at the mmtv promoter is highly dynamic, with an initial increase ... | 2007 | 17227884 |
| pleiotrophin, a multifunctional tumor promoter through induction of tumor angiogenesis, remodeling of the tumor microenvironment, and activation of stromal fibroblasts. | pleiotrophin (ptn, ptn) is a widely expressed, developmentally regulated 136 amino acid secreted heparin-binding cytokine. it signals through a unique signaling pathway; the ptn receptor is the transmembrane receptor protein tyrosine phosphatase (rptp)beta/zeta. rptpbeta/zeta is inactivated by ptn, which leads to increased tyrosine phosphorylation of the downstream targets of the ptn/rptpbeta/zeta signaling pathway. pleiotrophin gene expression is found in cells in early differentiation during d ... | 2007 | 18156802 |
| erbb-2 receptor cooperates with e6/e7 oncoproteins of hpv type 16 in breast tumorigenesis. | the erbb-2 receptor is overexpressed in roughly 30% of human breast cancers. moreover, approximately 50% of breast cancers are positive for high-risk human papillomaviruses (hpvs), specifically types 16 and 18. recently, we reported that erbb-2 cooperates with e6/e7 oncoproteins of hpv type 16 to induce neoplastic transformation of human normal oral epithelial cells. we also demonstrated that e6/e7 of hpv type 16 converts non-invasive breast cancer cells to an invasive form. in order to investig ... | 2007 | 18156804 |
| amino-biphosphonate-mediated mmp-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma. | balb-neut mice expressing an activated rat c-erbb-2/neu transgene under the mouse mammary tumor virus long terminal repeat show enhanced hematopoiesis with hyperproduction of myeloid-derived suppressor cells (mdsc) because of vascular endothelial growth factor (vegf) secreted by the tumor. here, we show that both tumor and stromal cells express matrix metalloproteinase-9 (mmp-9), thereby increasing the levels of pro-mmp-9 in the sera of tumor-bearing mice. treatment with amino-biphosphonates imp ... | 2007 | 18056472 |
| mouse mammary tumor virus-like gene sequences in breast cancer samples of mexican women. | previous reports related the presence of mouse mammary tumor virus (mmtv)-like gene sequences to human breast carcinoma. the aim of this study was to determine whether mmtv-like env gene sequences are present in breast cancer samples of mexican women and in breast and lung cancer cell lines. | 2007 | 17975321 |
| sequence-dependent nucleosome structure and stability variations detected by förster resonance energy transfer. | nucleosomes, the basic unit of eukaryotic chromosome structure, cover most of the dna in eukaryotes, including regulatory sequences. here, a recently developed förster resonance energy transfer approach is used to compare structure and stability features of sea urchin 5s nucleosomes and nucleosomes reconstituted on two promoter sequences that are nucleosomal in vivo, containing the yeast gal10 tata or the major transcription response elements from the mouse mammary tumor virus promoter. all thre ... | 2007 | 17269656 |
| retroviral vectors containing tet-controlled bidirectional transcription units for simultaneous regulation of two gene activities. | in this study retroviral self-inactivating (sin)-vectors were constructed, that allow simultaneous regulation of two genes by integration of bidirectional tet controlled transcription units. marker genes (luciferase and egfp) were expressed under the control of various bidirectional promoters p(tet)bis, in order to determine (i) the fraction of htta-1 cells exhibiting tight doxycycline (dox) dependent control; (ii) possible effects of the vector backbone on the regulation of gene transcription; ... | 2006 | 19565004 |
| chromatin remodeling and control of cell proliferation by progestins via cross talk of progesterone receptor with the estrogen receptors and kinase signaling pathways. | transcription from the mouse mammary tumor virus (mmtv) promoter can be induced by glucocorticoids or progestins. progesterone treatment of cultured cells carrying an integrated single copy of an mmtv transgene leads to recruitment of progesterone receptor (pr), swi/snf, and snf2h-related complexes to mmtv promoter. recruitment is accompanied by selective displacement of histones h2a and h2b from the nucleosome b. in nucleosomes assembled on promoter sequences, swi/snf displaces histones h2a and ... | 2006 | 17261755 |
| induction of progesterone target genes requires activation of erk and msk kinases and phosphorylation of histone h3. | how genes are regulated in the context of chromatin is a central question of biology. steroid hormones control gene expression via interaction of their receptors with target sequences on dna but can also activate cytoplasmic signaling cascades. here we report that rapid erk activation by progestins participates in induction of target genes by preparing the chromatin for transcription. five minutes after hormone treatment, erk activation leads to phosphorylation of the progesterone receptor (pr), ... | 2006 | 17081988 |
| expression of constitutively active notch1 in male genital tracts results in ectopic growth and blockage of efferent ducts, epididymal hyperplasia and sterility. | the notch signaling pathway is involved in a variety of developmental processes. here, we characterize the phenotypes developing in the reproductive organs of male transgenic (tg) mice constitutively expressing the activated mouse notch1 intracellular domain (notch1(intra)) under the regulatory control of the mouse mammary tumor virus (mmtv) long terminal repeat (ltr). tg expression was detected in testis, vas deferens and epididymis by northern blot analysis. in situ hybridization with a notch1 ... | 2006 | 17046738 |
| stromal and epithelial caveolin-1 both confer a protective effect against mammary hyperplasia and tumorigenesis: caveolin-1 antagonizes cyclin d1 function in mammary epithelial cells. | here, we investigate the role of caveolin-1 (cav-1) in breast cancer onset and progression, with a focus on epithelial-stromal interactions, ie, the tumor microenvironment. cav-1 is highly expressed in adipocytes and is abundant in mammary fat pads (stroma), but it remains unknown whether loss of cav-1 within mammary stromal cells affects the differentiated state of mammary epithelia via paracrine signaling. to address this issue, we characterized the development of the mammary ductal system in ... | 2006 | 17071600 |
| a role of the amino-terminal (n) and carboxyl-terminal (c) interaction in binding of androgen receptor to chromatin. | the n-terminal domain of ar is known to engage a hormone-dependent interaction with its c-terminal ligand-binding domain, and this n/c interaction is known to modulate ar transcriptional activity. using xenopus oocytes as a model system to study transcriptional regulation in chromatin, we found that two previously reported n/c interaction-defective ar mutants, one with deletion of 23fqnlf27(ardeltaf) and one with a gly 21 to glu mutation (arg21e), were surprisingly inactive in activating transcr ... | 2006 | 16373397 |
| structurally distinct ligand-binding or ligand-independent notch1 mutants are leukemogenic but affect thymocyte development, apoptosis, and metastasis differently. | we previously found that provirus insertion in t cell tumors of mouse mammary tumor virus/c-myc transgenic (tg) mice induced two forms of notch1 mutations. type i mutations generated two truncated molecules, one intracellular (ic) (notch1(ic)) and one extracellular (notch1(ec)), while in type ii mutations notch1 was deleted of its c terminus (notch1(deltact)). we expressed these mutants in tg mice using the cd4 promoter. both notch1(ic) and notch1(deltact), but not notch1(ec), tg mice developed ... | 2006 | 16887975 |
| determination of androgen bioactivity in human serum samples using a recombinant cell based in vitro bioassay. | the present study describes the development and optimization of a cell-based reporter assay for the determination of androgen bioactivity levels in human serum samples. towards this end, human embryonic kidney (hek) 293 cells were cotransfected with two plasmids, one encoding the mouse mammary tumor virus (mmtv)-driven luciferase reporter gene and the other the sv40 promoter-driven human androgen receptor (ar), and a stable cell line, expressing human ar and androgen-responsive luciferase was es ... | 2006 | 16893644 |
| epithelial-specific and stage-specific functions of insulin-like growth factor-i during postnatal mammary development. | postnatal development of the mammary gland requires interactions between the epithelial and stromal compartments, which regulate actions of hormones and growth factors. igf-i is expressed in both epithelial and stromal compartments during postnatal development of the mammary gland. however, little is known about how local expression of igf-i in epithelium or stroma regulates mammary growth and differentiation during puberty and pregnancy-induced alveolar development. the goal of this study was t ... | 2006 | 16901968 |
| tumor cell-derived and macrophage-derived cathepsin b promotes progression and lung metastasis of mammary cancer. | proteolysis in close vicinity of tumor cells is a hallmark of cancer invasion and metastasis. we show here that mouse mammary tumor virus-polyoma middle t antigen (pymt) transgenic mice deficient for the cysteine protease cathepsin b (ctsb) exhibited a significantly delayed onset and reduced growth rate of mammary cancers compared with wild-type pymt mice. lung metastasis volumes were significantly reduced in pymt;ctsb(+/-), an effect that was not further enhanced in pymt;ctsb(-/-) mice. further ... | 2006 | 16707449 |
| endogenous mmtv proviruses induce susceptibility to both viral and bacterial pathogens. | most inbred mice carry germline proviruses of the retrovirus, mouse mammary tumor virus (mmtv) (called mtvs), which have multiple replication defects. a balb/c congenic mouse strain lacking all endogenous mtvs (mtv-null) was resistant to mmtv oral and intraperitoneal infection and tumorigenesis compared to wild-type balb/c mice. infection of mtv-null mice with an mmtv-related retrovirus, type b leukemogenic virus, also resulted in severely reduced viral loads and failure to induce t-cell lymphom ... | 2006 | 17140288 |
| selection of early-occurring mutations dictates hormone-independent progression in mouse mammary tumor lines. | mice harboring three mouse mammary tumor virus (mmtv) variants develop pregnancy-dependent (pd) tumors that progress to pregnancy-independent (pi) behavior through successive passages. herein, we identified 10 predominant insertions in pi transplants from 8 independent tumor lines. these mutations were also detected in small cell populations in the early pd passages. in addition, we identified a new viral insertion upstream of the gene rspo3, which is overexpressed in three of the eight independ ... | 2006 | 16971449 |
| overexpression of aurora kinase a in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. | aurora-a/stk15/btak, which encodes a centrosome-associated kinase, is amplified and overexpressed in multiple types of human tumors, including breast cancer. however, the causal relationship between overexpression of aurora-a and tumorigenesis has not been fully established due to contradictory data obtained from different experimental systems. to investigate this, we generated a mouse strain that carries an mmtv-aurora-a transgene. we showed that all the mmtv-aurora-a mice displayed enhanced br ... | 2006 | 16715125 |
| differentiation-induced cleavage of cutl1/cdp generates a novel dominant-negative isoform that regulates mammary gene expression. | cutl1/ccaat displacement protein (cdp) is a transcriptional repressor of mouse mammary tumor virus (mmtv), a betaretrovirus that is a paradigm for mammary-specific gene regulation. virgin mammary glands have high levels of full-length cdp (200 kda) that binds to negative regulatory elements (nres) to repress mmtv transcription. during late pregnancy, full-length cdp levels decline, and a 150-kda form of cdp (cdp150) appears concomitantly with a decline in dna-binding activity for the mmtv nres a ... | 2006 | 17015474 |
| autocrine pdgfr signaling promotes mammary cancer metastasis. | metastasis is the major cause of cancer morbidity, but strategies for direct interference with invasion processes are lacking. dedifferentiated, late-stage tumor cells secrete multiple factors that represent attractive targets for therapeutic intervention. here we show that metastatic potential of oncogenic mammary epithelial cells requires an autocrine pdgf/pdgfr loop, which is established as a consequence of tgf-beta-induced epithelial-mesenchymal transition (emt), a faithful in vitro correlat ... | 2006 | 16741576 |
| myc is a notch1 transcriptional target and a requisite for notch1-induced mammary tumorigenesis in mice. | to explore the potential involvement of aberrant notch1 signaling in breast cancer pathogenesis, we have used a transgenic mouse model. in these animals, mouse mammary tumor virus ltr-driven expression of the constitutively active intracellular domain of the notch1 receptor (n1(ic)) causes development of lactation-dependent mammary tumors that regress upon gland involution but progress to nonregressing, invasive adenocarcinomas in subsequent pregnancies. up-regulation of myc in these tumors prom ... | 2006 | 16751266 |
| hdac1 acetylation is linked to progressive modulation of steroid receptor-induced gene transcription. | although histone deacetylases (hdacs) are generally viewed as corepressors, we show that hdac1 serves as a coactivator for the glucocorticoid receptor (gr). furthermore, a subfraction of cellular hdac1 is acetylated after association with the gr, and this acetylation event correlates with a decrease in promoter activity. hdac1 in repressed chromatin is highly acetylated, while the deacetylase found on transcriptionally active chromatin manifests a low level of acetylation. acetylation of purifie ... | 2006 | 16762839 |
| alteration of t-cell receptor repertoires during thymic t-cell development. | the majority of thymocytes die in the thymus, whereas small populations of t cells that are able to specifically recognize an antigen are considered to survive. although the thymic selection is thought to have a profound effect on t-cell receptor (tcr) repertoire, little is known how tcr repertoire is formed during the thymocyte developmental process. we examined tcralpha- and beta-chain variable regions (tcrav and tcrbv) repertoire in thymic t-cell subpopulations from mice bearing different maj ... | 2006 | 16784491 |
| the htlv-i p30 interferes with tlr4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. | whereas adaptive immunity has been extensively studied, very little is known about the innate immunity of the host to htlv-i infection. htlv-i-infected atl patients have pronounced immunodeficiency associated with frequent opportunistic infections, and in these patients, concurrent infections with bacteria and/or parasites are known to increase risks of progression to atl. the toll-like receptor-4 (tlr4) activation in response to bacterial infection is essential for dendritic cell maturation and ... | 2006 | 16785240 |
| tissue-specific sensitivity to aid expression in transgenic mouse models. | activation-induced cytidine deaminase (aid), an enzyme with homology to members of the apobec family, is involved in somatic hypermutation (shm) of immunoglobulin (ig) genes, either by direct deamination of dna or by an indirect action through its putative rna editing activity. aid is able to mutate both ig-like reporter constructs and selected non-ig genes in normal b cells and in other cells when ectopically overexpressed in mammalian cells and transgenic mice. however, in spite of the fact th ... | 2006 | 16787714 |
| viral immunoreceptor tyrosine-based activation motif (itam)-mediated signaling in cell transformation and cancer. | viruses frequently co-opt host cell pathways to enhance their propagation or to enable latent infection. certain receptors expressed by hematopoietic cells have immunoreceptor tyrosine-based activation motifs (itams) in their cytoplasmic domains that initiate cellular activation, proliferation and differentiation. some viruses have evolved, or acquired from their host, genes that encode itam-bearing proteins. these itam-bearing viral proteins have been implicated in cellular transformation in vi ... | 2006 | 16815013 |
| parallel analysis of transcript and translation profiles: identification of metastasis-related signal pathways differentially regulated by drug and genetic modifications. | tumor metastasis is a complex multistep process normally involving dysregulation of multiple signal transduction pathways. in this study, we developed a novel approach to efficiently define dysreguated pathways associated with metastasis by comparing global gene and protein expressions of two distinct metastasis-suppressed models. consequently, we identified common features shared by the two models which are potentially associated with metastasis. the efficiency of metastasis from the highly agg ... | 2006 | 16823962 |
| challenge with mammary tumor cells expressing mhc class ii and cd80 prevents the development of spontaneously arising tumors in mmtv-neu transgenic mice. | the her-2/neu oncogene has been implicated in human and mouse breast cancer. indeed, transgenic mmtv-neu mice expressing this oncogene from the mammary tumor virus long terminal repeat develop spontaneous mammary tumors and die within 1 year of life. we have expressed the class ii transactivator (ciita) and/or the costimulatory molecule cd80 (b7.1) in a mammary carcinoma cell line (mcneua) derived from these mice. class ii transactivator directs the expression of mhc class ii and the machinery f ... | 2006 | 16841083 |
| single-cell analysis of glucocorticoid receptor action reveals that stochastic post-chromatin association mechanisms regulate ligand-specific transcription. | the glucocorticoid receptor (gr) dynamically interacts with response elements in the mouse mammary tumor virus (mmtv) promoter to regulate steroid-dependent transcription. in a clonal mammary carcinoma cell line containing a tandem array of mmtv promoter-reporter gene cassettes integrated at a single genomic locus, direct binding of a green fluorescent protein (gfp)-gr fusion protein to the mmtv regulatory elements can be observed in living cells. after ligand treatment, mmtv-dependent transcrip ... | 2006 | 16873444 |
| transgenic mice expressing the p75 ccaat-displacement protein/cut homeobox isoform develop a myeloproliferative disease-like myeloid leukemia. | the p75 ccaat-displacement protein/cut homeobox (cdp/cux) isoform was previously reported to be overexpressed in human breast cancers. to investigate its oncogenic potential, we engineered two transgenic mouse lines expressing p75 cdp/cux under the control of the mouse mammary tumor virus-long terminal repeat. the fvb strain of mouse is generally used in the generation of mouse models for breast cancer. the transgene was introduced into the hprt locus of 129/ola embryonic stem cells and, followi ... | 2006 | 17018605 |
| a common polymorphism in the mineralocorticoid receptor modulates stress responsiveness. | mineralocorticoid receptors (mr) mediate the action of aldosterone on sodium resorption in kidney tubular cells, but in brain they respond to the glucocorticoid cortisol in stress regulation and cognitive processes. | 2006 | 17018659 |
| the combination of the rexinoid, lg100268, and a selective estrogen receptor modulator, either arzoxifene or acolbifene, synergizes in the prevention and treatment of mammary tumors in an estrogen receptor-negative model of breast cancer. | we tested whether a selective estrogen receptor modulator (serm) and a rexinoid are active for prevention and treatment in the mouse mammary tumor virus-neu mouse model of estrogen receptor-negative breast cancer. | 2006 | 17020999 |
| enhancement of the streptotag method for isolation of endogenously expressed proteins with complex rna binding targets. | streptotag is a novel affinity chromatography-based method for the isolation of high- and low-affinity rna binding proteins. originally it was shown possible to isolate recombinant protein from yeast or bacterial extracts using small, specific, well-characterised rna binding targets. here we show that using an enhanced aptamer it is not only possible to efficiently immobilise large, highly structured rna binding targets onto the streptomycin columns but also that the streptotag method can be use ... | 2006 | 16604572 |
| interactive effects of selenium and chromium on mammary tumor development and growth in mmtv-infected female mice and their relevance to human cancer. | evidence for interactive effects of chromium and selenium on the appearance of mammary tumors was obtained by exposing female virgin c3h mice infected with the murine mammary tumorvirus (mmtv) to subtoxic levels of cr [as cr(iii) nitrate] and se (as sodium selenite) in the supply water. cr counteracted the inhibitory effect of se on tumor development in a dose-dependent manner, shortened the tumor latency period, and accelerated tumor growth rates. exposure to cr also altered the levels of se in ... | 2006 | 16632896 |
| p130cas as a new regulator of mammary epithelial cell proliferation, survival, and her2-neu oncogene-dependent breast tumorigenesis. | to investigate the mechanisms through which p130cas adaptor protein is linked to tumorigenesis, we generated mouse mammary tumor virus (mmtv)-p130cas mice overexpressing p130cas in the mammary gland. mmtvp130cas transgenic mice are characterized by extensive mammary epithelial hyperplasia during development and pregnancy and by delayed involution at the end of lactation. these phenotypes are associated with activation of src kinase, extracellular signal-regulated kinase 1/2, mitogen-activated pr ... | 2006 | 16651418 |
| analysis of binding at a single spatially localized cluster of binding sites by fluorescence recovery after photobleaching. | cells contain many subcellular structures in which specialized proteins locally cluster. binding interactions within such clusters may be analyzed in live cells using models for fluorescence recovery after photobleaching (frap). here we analyze a three-dimensional frap model that accounts for a single spatially localized cluster of binding sites in the presence of both diffusion and impermeable boundaries. we demonstrate that models completely ignoring the spatial localization of binding yield p ... | 2006 | 16679358 |
| transgenic mice with mammary gland targeted expression of human cortactin do not develop (pre-malignant) breast tumors: studies in mmtv-cortactin and mmtv-cortactin/-cyclin d1 bitransgenic mice. | in human breast cancers, amplification of chromosome 11q13 correlates with lymph node metastasis and increased mortality. to date, two genes located within this amplicon, ccnd1 and ems1, were considered to act as oncogenes, because overexpression of both proteins, respectively cyclin d1 and cortactin, correlated well with 11q13 amplification. cyclin d1 is involved in cell cycle regulation and the f-actin-binding protein cortactin in cytoskeletal dynamics and cell migration. to study the role of ... | 2006 | 16536875 |
| progesterone regulates hla-g gene expression through a novel progesterone response element. | we have previously demonstrated that progesterone has a stimulatory effect on hla-g gene expression. because this effect was abolished by the anti-progestin, ru486, we hypothesize that this effect is through receptor-mediated up-regulation of the hla-g gene. the objective of this study was to explore the molecular mechanisms of this effect. | 2006 | 16684846 |
| presence of mouse mammary tumour-like virus gene sequences may be associated with morphology of specific human breast cancer. | mouse mammary tumour virus (mmtv) has a proven role in breast carcinogenesis in wild mice and genetically susceptible in-bred mice. mmtv-like env gene sequences, which indicate the presence of a replication-competent mmtv-like virus, have been identified in some human breast cancers, but rarely in normal breast tissues. however, no evidence for a causal role of an mmtv-like virus in human breast cancer has emerged, although there are precedents for associations between specific histological char ... | 2006 | 16698952 |
| potent in vivo anti-breast cancer activity of in-2001, a novel inhibitor of histone deacetylase, in mmtv/c-neu mice. | a novel synthetic inhibitor of histone deacetylase (hdac), 3-(4-dimethylaminophenyl)-n-hydroxy-2-propenamide (in-2001), was examined for its antitumor activity and for the underlying molecular mechanisms of any such activity. in-2001 effectively inhibited cellular hdac activity (ic(50), 5.42 nmol/l) in mcf-7 human breast cancer cells. based on the western blot analysis, this hdac inhibitory effect of in-2001 was confirmed by an increase in histone h4 acetylation from the in-2001-treated breast c ... | 2006 | 16707467 |
| role of src kinases in neu-induced tumorigenesis: challenging the paradigm using csk homologous kinase transgenic mice. | amplification of the her-2/neu (erbb2) gene is observed in approximately 30% of human breast cancers, correlating with a poor clinical prognosis. src kinases are also involved in the etiology of breast cancer, and their activation was suggested to be necessary for neu-induced oncogenesis. to address whether src activity is essential for neu-mediated tumorigenesis, we used a physiologic inhibitor of src kinase activity, the csk homologous kinase (chk), expressed as a mammary tissue-specific trans ... | 2006 | 16740714 |
| mmtv-like sequences in human breast cancer: a fluorescent pcr/laser microdissection approach. | the hypothesis that a retrovirus homologous to the mouse mammary tumour virus (mmtv) is involved in human breast cancer aetiology has fascinated scientists from many years, but it has never been convincingly demonstrated. renewed interest in this hypothesis developed when an mmtv env gene-like sequence was found in 38% of human breast cancer tissues. whereas some subsequent studies confirmed these findings, others did not. the main reasons for this discrepancy, among others, are the different se ... | 2006 | 16710841 |