| muc1 affects c-src signaling in pyv mt-induced mammary tumorigenesis. | muc1 is an integral membrane mucin glycoprotein that is normally expressed on the apical surface of most simple, secretory epithelia and hematopoietic cells. overexpression of aberrantly glycosylated muc1 is a hallmark of many carcinomas including 90% of breast carcinomas. muc1 has been shown to bind to c-src tyrosine kinase in vitro, whereby c-src phosphorylates the muc1 cytoplasmic domain at a yekv motif. c-src is an extensively studied nonreceptor tyrosine kinase implicated in mammary tumorig ... | 2005 | 15897873 |
| human cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma. | human cripto-1 (cr-1) is overexpressed in approximately 80% of human breast, colon and lung carcinomas. mouse cr-1 upregulation is also observed in a number of transgenic (tg) mouse mammary tumors. to determine whether cr-1 can alter mammary gland development and/or may contribute to tumorigenesis in vivo, we have generated tg mouse lines that express human cr-1 under the transcriptional control of the mouse mammary tumor virus (mmtv). stable tg mmtv/cr-1 fvb/n lines expressing different levels ... | 2005 | 15897912 |
| a novel, mouse mammary tumor virus encoded protein with rev-like properties. | we have identified a novel, multiple spliced, subgenomic mrna species in mmtv producing cells of different origin containing an open reading frame encoding a 39-kda rev-like protein, rem (regulator of expression of mmtv). an egfp-rem fusion protein is shown to be predominantly in the nucleolus. further leptomycin b inhibits the nuclear export of nonspliced mmtv transcripts, implicating rem in nuclear export by the crm1 pathway in mmtv. rem is thus reminiscent of the rec protein from the related ... | 2005 | 15914215 |
| a defective viral superantigen-presenting phenotype in hla-dr transfectants is corrected by ciita. | activation of t lymphocytes by mouse mammary tumor virus superantigen (vsag) requires binding to mhc class ii molecules. the subcellular location where functional interactions occur between mhc class ii molecules and vsags is still a matter of debate. to gain further insight into this issue, we have used human epithelial hela cells expressing hla-dr1. surprisingly, the human cells were unable to present transfected vsag7 or vsag9 to a series of murine t cell hybridomas. the defect is not related ... | 2005 | 15944254 |
| an mhc class ib-restricted tcr that cross-reacts with an mhc class ia molecule. | tcr transgenic 6c5 t cells recognize an insulin b chain epitope presented by the nonclassical class i mhc molecule, qa-1(b). positive selection of these t cells was shown previously to require qa-1(b). despite dedicated specificity for qa-1(b), evidence presented in the current study indicates that 6c5 t cells can cross-recognize a classical class i molecule. clonal deletion was observed unexpectedly in 6c5.h-2(bxq) mice, which do not express i-e mhc class ii molecules and thus should not be sub ... | 2005 | 15944277 |
| cripto-1: an oncofetal gene with many faces. | human cripto-1 (cr-1), a member of the epidermal growth factor (egf)-cfc family, has been implicated in embryogenesis and in carcinogenesis. during early vertebrate development, cr-1 functions as a co-receptor for nodal, a transforming growth factor beta (tgfbeta) family member and is essential for mesoderm and endoderm formation and anterior-posterior and left-right axis establishment. in adult tissues, cr-1 is expressed at a low level in all stages of mammary gland development and expression i ... | 2005 | 15949532 |
| dissociated glucocorticoids equipotently inhibit cytokine- and camp-induced matrix degrading proteases in rat mesangial cells. | dissociated glucocorticoids are synthetic ligands of the glucocorticoid receptor (gr) and which discriminate between transrepression and transactivation. these compounds were predicted to have large therapeutic benefits when compared to conventional glucocorticoids because of reduced side effects. in this study, we compared the transrepressive properties of different dissociated glucocorticoids on the interleukin-1beta (il-1beta)-activated metalloproteinase-9 (mmp-9) and tissue plasminogen activ ... | 2005 | 15963473 |
| influence of camp on reporter bioassays for dioxin and dioxin-like compounds. | in reporter assays for detection of dioxins, the dioxin-responsive element (dre) is generally used as a sensor sequence. in several systems, the cyp1a1 promoter containing dres (dre(cyp)) is inserted into a part of the long terminal repeat of mouse mammary tumor virus (ltr(mmtv)) to improve sensitivity of assays. we found that dre(cyp)-ltr(mmtv) responds not only to dioxins and dioxin-like compounds but also to forskolin, a camp-elevating agent. this effect was dose-dependent and reproduced by o ... | 2006 | 15972221 |
| mammary carcinoma provides highly tumourigenic and invasive reactive stromal cells. | the progression of a lesion to a carcinoma is dependent on the engagement of 'reactive stroma' that provides structural and vascular support for tumour growth and also leads to tissue reorganization and invasiveness. the composition of reactive stroma closely resembles that of granulation tissue, and myofibroblasts are thought to play a critical role in driving the stromal reaction of invasive tumours as well as of physiological wound repair. in the present work, we established a myofibroblast-l ... | 2005 | 15975963 |
| the structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions. | nuclear receptors (nrs) are ligand-regulated transcription factors important in human physiology and disease. in certain nrs, including the androgen receptor (ar), ligand binding to the carboxy-terminal domain (lbd) regulates transcriptional activation functions in the lbd and amino-terminal domain (ntd). the basis for ntd-lbd communication is unknown but may involve ntd-lbd interactions either within a single receptor or between different members of an ar dimer. here, measurement of fret betwee ... | 2005 | 15994236 |
| direct agonist/antagonist functions of dehydroepiandrosterone. | dehydroepiandrosterone (dhea) exhibits peak adrenal secretion in the fetus at term and around age 30 yr in the adult. levels then progressively decline, which is associated with decreased levels of testosterone, dihydrotestosterone, and estrogen in peripheral tissues. dhea supplementation in postmenopausal women increases bone formation and density, an effect mainly attributed to peripheral conversion to sex hormones. in this study, we tested dhea for direct effects on the androgen (ar) and estr ... | 2005 | 15994348 |
| kinase-inactive glycogen synthase kinase 3beta promotes wnt signaling and mammary tumorigenesis. | recent studies have implicated ectopic activation of the wnt pathway in many human cancers, including breast cancer. beta-catenin is a critical coactivator in this signaling pathway and is regulated in a complex fashion by phosphorylation, degradation, and nuclear translocation. glycogen synthase kinase 3beta (gsk3beta) phosphorylation of the nh2-terminal domain of beta-catenin targets it for ubiquitination and proteosomal degradation. we hypothesized that expression of kinase-inactive gsk3beta ... | 2005 | 15994955 |
| design and synthesis of new nonsteroidal glucocorticoid modulators through application of an "agreement docking" method. | structurally related glucocorticoid receptor (gr) binders were docked into the gr active site to select the binding mode closest to the true docking mode. this process, termed an "agreement docking method", led to the design of tetrahydronaphthalene 9. the method was validated by the syntheses of 9 and related analogues, which are potent binders of gr. 15a is a partial agonist while 9e and 15a are micromolar antagonists in a mouse mammary tumor virus transactivation assay. | 2005 | 15999989 |
| changes in attitude, changes in latitude: nuclear receptors remodeling chromatin to regulate transcription. | nuclear receptors (nrs) are a large family of ligand-dependent transcription factors that regulate important physiological processes. to activate or repress genes assembled naturally as chromatin, nrs recruit two distinct enzymatic activities, namely histone-modifying enzymes and atp-dependent chromatin remodeling complexes, to alter local chromatin structure at target gene promoters. in this review, we examine the functional relationship between atp-dependent chromatin remodeling complexes and ... | 2006 | 16002433 |
| gene expression analysis reveals a strong signature of an interferon-induced pathway in childhood lymphoblastic leukemia as well as in breast and ovarian cancer. | on the basis of epidemiological studies, infection was suggested to play a role in the etiology of human cancer. while for some cancers such a role was indeed demonstrated, there is no direct biological support for the role of viral pathogens in the pathogenesis of childhood leukemia. using a novel bioinformatic tool that alternates between clustering and standard statistical methods of analysis, we performed a 'double-blind' search of published gene expression data of subjects with different ch ... | 2005 | 16007187 |
| a new common integration site, int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences. | a novel common integration site for the mouse mammary tumor virus (mmtv) was identified (designated int7) in five independently arising mouse mammary tumors. the insertion sites all cluster within a 1-kb region that is 2 to 3 kb 5' of the transcription initiation site of a gene, 2610028f08rik, whose gene product contains furin-like and thrombospondin-like sequences. expression of int7 is normally very low or silent during various stages of mammary gland development, but mmtv integration at this ... | 2005 | 16014973 |
| hiv-1 rev can specifically interact with mmtv rna and upregulate gene expression. | we present evidence that the hiv-1 rev protein can heterologously regulate expression of the simple beta retrovirus mouse mammary tumour virus (mmtv). up to 10-fold upregulation was seen in a functional assay system when specific mmtv sequences were substituted for the hiv-1 rev responsive element (rre). rna gel shift analysis showed that purified recombinant rev could specifically bind to mmtv unique region 3 prime (u3) rna and that these sequences could compete for wild-type rev-rre binding ap ... | 2005 | 16023306 |
| tlr-4 regulates cd8+ t cell trapping in the liver. | mammalian tlrs are understood primarily as an activating system for innate and adaptive immunity, but have also been implicated in sensing cellular damage and in promoting intestinal integrity. in this study we show that tlr-4 also controls the in vivo distribution of activated cd8+ t cells. the liver is a site for trapping and apoptosis of activated cd8+ t cells during systemic immune responses, but the reason for this is unknown. in this study we tested the hypothesis that the liver's constant ... | 2005 | 16034104 |
| caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis. | a significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. we have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, ca ... | 2004 | 16035617 |
| sequence-specific minor groove binding ligands as potential regulators of gene expression in xenopus laevis oocytes. | the mouse mammary tumor virus (mmtv) promoter is induced by glucocorticoid hormone. a robust hormone- and receptor-dependent gene activation could be reproduced in xenopus laevis oocytes. the homogeneous response in this system allowed a detailed analysis of the dna-protein interactions following hormone activation. the strategy of artificial regulating of gene activity by sequence-specific minor groove binding ligands is very attractive. we have synthesized and studied the interaction with dna ... | 2005 | 16060693 |
| mouse mammary tumor virus infects human cells. | mouse mammary tumor virus (mmtv) has long been speculated to be involved in human breast cancer and more recently in human primary biliary cirrhosis. despite complete proviral sequences markedly homologous to mmtv being identified in human breast cancer tissue, no convincing evidence has been presented to date that mmtv can infect human cells. using both wild-type and a genetically marked virus (mmtv-egfp), we show here the successful infection of a number of different human cells by mmtv. furth ... | 2005 | 16061645 |
| solution afm studies of human swi-snf and its interactions with mmtv dna and chromatin. | atp-dependent nucleosome remodeling complexes are crucial for relieving nucleosome repression during transcription, dna replication, recombination, and repair. remodeling complexes can carry out a variety of reactions on chromatin substrates but precisely how they do so remains a topic of active inquiry. here, a novel recognition atomic force microscopy (afm) approach is used to characterize human swi-snf (hswi-snf) nucleosome remodeling complexes in solution. this information is then used to lo ... | 2005 | 16100261 |
| mouse mammary tumor virus env-derived peptide associates with nucleolar targets in lymphoma, mammary carcinoma, and human breast cancer. | we have previously shown that the leader peptide (p14) of the env-precursor of mouse mammary tumor virus is translocated into the nucleoli of murine t cell lymphomas that harbor this virus. using a polyclonal antibody against recombinant p14, we show here that p14 is also localized to the nucleoli of murine mammary carcinomas and some human breast cancer samples. affinity purification studies define a number of proteins, mostly nucleolar, that bind p14. taken together, these findings point towar ... | 2005 | 16103073 |
| the breast cancer susceptibility gene brca1 regulates progesterone receptor signaling in mammary epithelial cells. | the progesterone receptor (pr) plays roles in normal mammary development and breast cancer formation, where it may exert both stimulatory and inhibitory actions. previously, the breast cancer susceptibility gene product brca1 was found to interact with and inhibit the transcriptional activity of estrogen receptor-alpha. in this study, we found that exogenous wild-type brca1 inhibited the activity of the pr in transient transfection assays utilizing a mouse mammary tumor virus-luc reporter. wild- ... | 2006 | 16109739 |
| [establishment of reporter gene-based assays for the identification of (anti) androgenic effects of chemicals in cho cells]. | develop reporter gene-based assays for the identification of (anti) androgenic effects of chemicals in cho cells, explore the antiandrogenic effects of 2,4-ddt and methoxychlor. | 2005 | 16111029 |
| androgen receptor activities of p,p'-dde, fenvalerate and phoxim detected by androgen receptor reporter gene assay. | in this study, we have developed a transient human androgen receptor (har) reporter gene assay using african monkey kidney cell line cv-1. the assay displayed appropriate response to the known androgen receptor (ar) agonist 5alpha-dihydrotestosterone (dht) and ar antagonist nilutamide. dht induced ar-mediated transcriptional activity in a concentration-dependent manner with median effective concentration (ec(50)) value of 3.90 x 10(-10) m. nilutamide exhibited potent antiandrogenic activity with ... | 2006 | 16125883 |
| evaluation of cell-based assays for steroid nuclear receptors delivered by recombinant baculoviruses. | the authors describe the use of modified baculoviruses containing mammalian expression cassettes (bacmam technology) in steroid nuclear receptor reporter assays designed for screening and profiling agonist and antagonist compounds. baculo-viruses were constructed that express full-length human genes for mineralocorticoid receptor (mr), glucocorticoid receptor (gr), progesterone receptor a (pr-a), and progesterone receptor b (pr-b) from the cytomegalovirus immediate early promoter. a virus carryi ... | 2005 | 16129777 |
| effect of lipopolysaccharide and antidepressant drugs on glucocorticoid receptor-mediated gene transcription. | it has been hypothesized that pro-inflammatory response and hyperactivity of hypothalamic-pituitary-adrenocortical axis (hpa) are involved in the pathogenesis of depression. hyperactivity of hpa axis results probably from deregulation of glucocorticoid receptor function and impairment of the control mechanism of glucocorticoid secretion. previously, we found that antidepressants inhibited glucocorticoid receptor (gr) function under the in vitro condition. in order to study a role of some mediato ... | 2005 | 16129923 |
| abundant authentic mmtv-env production from a recombinant provirus lacking the major ltr promoter. | as for all retroviruses, the env mrna is thought to be a singly spliced product of the full-length transcript from the p1 promoter in the mmtv provirus. however, we show that envelope proteins can be produced in an inducible manner in the absence of the p1 promoter from an otherwise complete provirus. furthermore, we demonstrate in both reporter assays and the proviral context that the r region is necessary for protein production in transiently transfected cells and in a number of independent, s ... | 2005 | 16140354 |
| mechanism of action of hic-5/androgen receptor activator 55, a lim domain-containing nuclear receptor coactivator. | hic-5/androgen receptor (ar) coactivator 55 (ara55) is a group iii lim domain protein that functions as a nuclear receptor coactivator. in the present study, we examined the mechanism by which hic-5/ara55 potentiates glucocorticoid receptor (gr) transactivation in the a1-2 derivative of t47d breast cancer cells. hic-5/ara55 is an important component of gr-coactivator complexes in a1-2 cells because ablation of hic-5/ara55 expression by rna interference-mediated silencing reduced gr transactivati ... | 2006 | 16141357 |
| conversion of mouse mammary tumor virus to a lymphomagenic virus. | type b leukemogenic virus is a variant of mouse mammary tumor virus (mmtv) that causes thymic lymphomas rather than mammary tumors in mice. we demonstrate that conversion of a mammotropic mmtv to a t-cell-tropic virus requires two alterations in the long terminal repeat: (i) acquisition of a t-cell-specific enhancer and (ii) loss of transcriptional repression through deletion of negative regulatory elements (nres) or by suppression of nre activity after appropriate positioning of the enhancer. | 2005 | 16160187 |
| changes in gene expression during the development of mammary tumors in mmtv-wnt-1 transgenic mice. | in human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ, invasive cancer, and metastasis. the changes in gene expression associated with this stepwise progression are unclear. mice transgenic for mouse mammary tumor virus (mmtv)-wnt-1 exhibit discrete steps of mammary tumorigenesis, including hyperplasia, invasive ductal carcinoma, and distant metastasis. these mice might therefore be useful models for discovering changes in gene expression during ... | 2005 | 16207355 |
| the association between breast cancer and lymphoma. | | 2005 | 16224443 |
| androgen inducibility of fgf8 in shionogi carcinoma 115 cells correlates with an adjacent t(5;19) translocation. | fgf8 (fibroblast growth factor 8) was initially cloned from a mouse mammary tumor cell line derived from the androgen-dependent shionogi carcinoma 115. the androgen-inducible expression of fgf8 in this tumor controls its androgen-dependent phenotype, thus stimulating interest in this gene as a possible factor in human prostate cancer and other androgen-sensitive cancers. however, apart from shionogi carcinoma 115, the androgen inducibility of fgf8 is controversial. in the present study, having n ... | 2006 | 16252261 |
| relb/p52 nf-kappab complexes rescue an early delay in mammary gland development in transgenic mice with targeted superrepressor ikappab-alpha expression and promote carcinogenesis of the mammary gland. | classical nf-kappab (p65/p50) transcription factors display dynamic induction in the mammary gland during pregnancy. to further elucidate the role of nf-kappab factors in breast development, we generated a transgenic mouse expressing the ikappab-alpha s32/36a superrepressor (sr) protein under control of the mouse mammary tumor virus (mmtv) long terminal repeat promoter. a transient delay in mammary ductal branching was observed in mmtv-sr-ikappab-alpha mice early during pregnancy at day 5.5 (d5. ... | 2005 | 16260626 |
| complex agonist-like properties of ici 182,780 (faslodex) in human breast cancer cells that predominantly express progesterone receptor-b: implications for treatment resistance. | ici 182,780 (faslodex), considered a pure anti-estrogen, is approved for treatment of post-menopausal breast cancer patients who fail to respond to tamoxifen therapy. we recently reported that, like mifepristone, ici 182,780 exhibits anti-progestin activity, blocking the progestin-dependent increase in endogenous vascular endothelial growth factor (vegf) mrna and protein release. some anti-progestins have partial agonist-like activity in breast cancer cells expressing high levels of progesterone ... | 2005 | 16273221 |
| induction of murine leukemia and lymphoma by dominant negative retinoic acid receptor alpha. | acute promyelocytic leukemia (apl) is invariably associated with chromosomal translocation to retinoic acid receptor alpha (raralpha) locus. in a vast majority of cases, raralpha translocates to and fuses with the promyelocytic leukemia (pml) gene. it was thought that the fusion protein pml-raralpha acts as a double dominant negative mutant to inhibit the pml and raralpha signaling. in an attempt to study the physiological role of retinoic acid in mammary gland development, we created a transgen ... | 2005 | 16273555 |
| human, rhesus macaque, and feline sequences highly similar to mouse mammary tumor virus sequences. | sequences highly similar (>95%) to the mouse mammary tumor virus (mmtv) env gene have been amplified from human dna samples, including dna samples from patients with breast cancer (bc) and persons who did not have bc. the sequences from human dna were distinct from the mmtv sequences used as controls in these pcr reactions, indicating that these results are not simply due to contamination. in addition to both, mouse and human-related sequences were also amplified from some monkey and cat genomic ... | 2005 | 16276510 |
| of mice, cats, and men: is human breast cancer a zoonosis? | mouse mammary tumor virus (mmtv), a member of the betaretroviridae, is the most common cause of breast cancer (bc) in mice. mmtv is transmitted in mice both in the germline as endogenous proviruses and exogenously as infectious virions. here, we review a variety of evidence accumulated for six decades that has suggested that a human homologue of mmtv may exist. the findings include recent studies from several independent laboratories that have detected sequences very closely related to mmtv in d ... | 2005 | 16276516 |
| mouse mammary tumor virus encodes a self-regulatory rna export protein and is a complex retrovirus. | mouse mammary tumor virus (mmtv) has been classified as a simple retrovirus with two accessory genes, dut and sag. cloned mmtv proviruses carrying a trimethoprim (trim) cassette in the envelope gene were defective for gag protein production and the nuclear export of unspliced gag-pol rna. complementation experiments indicated that a trans-acting product was responsible for the gag defect of such mutants. analysis of mmtv-infected cells revealed the presence of a novel, doubly spliced rna that en ... | 2005 | 16282474 |
| a direct test of potential roles for beta3 and beta5 integrins in growth and metastasis of murine mammary carcinomas. | alphavbeta3 or alphavbeta5 integrins are widely expressed on blood and endothelial cells. inhibition of the functions of these integrins has been reported to suppress neovascularization and tumor growth, suggesting that they may be critical modulators of angiogenesis. however, mice lacking these integrins exhibit extensive angiogenesis. tumors arising from s.c. injections of tumor cells into mice lacking one or both integrins show enhanced tumor growth compared with growth in control mice due to ... | 2005 | 16288021 |
| transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. | transforming acidic coiled coil 1 (tacc1) is a putative oncogene located within a breast cancer amplicon found on human chromosome 8p11. although tacc1 has been reported to transform fibroblasts, it is also down-regulated in a subset of mammary tumors treated with anthracyclin. here, we show that ectopic tacc1 overexpression can cooperate with ras to induce focus formation in murine fibroblast cultures and prevent death caused by overexpression of pten or a dominant-negative form of protein kina ... | 2005 | 16288026 |
| molecular and cellular basis of the retrovirus resistance in i/lnj mice. | previously, we showed that ifn-gamma elicited by mouse mammary tumor virus (mmtv) infection in i/lnj mice stimulated production of virus-neutralizing abs, mostly of the igg2a isotype. these abs coated virions secreted by infected i/lnj cells, and thus completely prevented virus transmission to offspring. however, the mechanism of virus neutralization by isotype-specific abs remained unknown. ab coating is capable of blocking virus infection by interfering with receptor-virus binding, by virus op ... | 2005 | 16301663 |
| mmtv accessory factor naf affects cellular gene expression. | mouse mammary tumour virus (mmtv) encodes a viral superantigen (sag) and a negative acting factor (naf) which share parts of their coding sequence. using 2-dimensional gel electrophoresis (2d-dige), we could show that at least 10 different cellular proteins were differentially expressed in naf positive cells. also, luciferase reporter expression was down-regulated in naf expressing cells independent of the promoter used and further experiments suggested that this effect was due in part to a decr ... | 2006 | 16310820 |
| the ubiquitin-specific protease usp10 modulates androgen receptor function. | the role of the ubiquitin/proteasome system in degrading nuclear hormone receptors and regulating their transcriptional function has emerged in the last few years. we identified the ubiquitin-specific protease usp10 as part of dna-bound androgen receptor (ar) complexes purified from nuclear extracts of pc-3 cells stably expressing the ar. the interaction between usp10 and the ar was confirmed by gst pull-down assays. fluorescence microscopy documented that usp10 was localised in the nucleus and ... | 2005 | 16368182 |
| 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 |
| effects of some new antidepressant drugs on the glucocorticoid receptor-mediated gene transcription in fibroblast cells. | antidepressant drugs are thought to counteract effects of hypercortisolemia, frequently associated with depression, by lowering cortisol level and by modifying the function of glucocorticoid receptors (gr). indeed, classical antidepressants inhibit corticosteroid-induced gene transcription in cell cultures. the aim of the present study was to investigate effects of new generation antidepressant drugs on gr function in mouse fibroblast cells (l929), stably transfected with mouse mammary tumor vir ... | 2005 | 16382195 |
| discovery and sar study of novel dihydroquinoline containing glucocorticoid receptor ligands. | we report the discovery of a novel class of glucocorticoid receptor (gr) ligands based on 1,2-dihydroquinoline molecular scaffold. the compounds exhibit good gr binding affinity and selectivity profile against other nuclear hormone receptors. | 2006 | 16386422 |
| transfection with steroid-responsive reporter constructs shows glucocorticoid rather than androgen responsiveness in cultured sertoli cells. | it remains unclear why it has proven so difficult to identify androgen target genes in cultured sertoli cells. given the lack of useful endogenous reporter genes, we studied the androgen and glucocorticoid responsiveness of these cells by transfection with three different steroid-responsive reporter constructs. the constructs were driven by the tyrosine aminotransferase steroid-responsive region (tat-gre4x-luc), the mouse mammary tumor virus promoter (mmtv-luc) and the pem homeobox gene proximal ... | 2006 | 16388947 |
| role of h1 phosphorylation in rapid gr exchange and function at the mmtv promoter. | photobleaching technology has demonstrated in live cells that the glucocorticoid receptor (gr) exchanges rapidly at the mouse mammary tumor virus (mmtv) promoter. gr rapid exchange at mmtv depends on chaperone and proteasome activity, and as suggested by several in vitro and in vivo biochemical approaches, may also involve chromatin remodeling activity. inhibition of h1 phosphorylation, chromatin remodeling and transcription from mmtv can be accomplished by long-term blocking of cdk2 protein kin ... | 2006 | 16397795 |
| human reporter gene assays: transcriptional activity of the androgen receptor is modulated by the cellular environment and promoter context. | the androgen receptor (ar) is a member of the nuclear receptor superfamily and mediates the physiological effects of androgens. androgens are essential for male development and disruption of androgen signaling may cause androgen-dependent developmental defects and/or tumors. here we present a comparative analysis of various model systems for the investigation of endocrine active compounds in human cell lines. we generated reporter plasmids containing androgen response elements derived from the h ... | 2006 | 16413649 |
| peg10 is a c-myc target gene in cancer cells. | the product of the imprinted gene paternally expressed gene-10 (peg10) has been reported to support proliferation in hepatocellular carcinomas, but how this gene is regulated has been an open question. we find that myc knockdown by rna interference suppresses peg10 expression in panc1 pancreatic carcinoma and hepg2 hepatocellular carcinoma cells and that knockdown of peg10 inhibits the proliferation of panc1, hepg2, and hep3b cells. conversely, peg10 was up-regulated by inducing c-myc expression ... | 2006 | 16423995 |
| p53 levels determine outcome during beta-catenin tumor initiation and metastasis in the mammary gland and male germ cells. | beta-catenin, an oncogene, and p53, a tumor suppressor, are common targets of mutation in human cancers. it has been observed that p53 is often inactivated in tumors involving beta-catenin activation. in an attempt to model this situation in vivo, we crossed the previously characterized mmtv-deltan-beta-catenin mouse with the p53 knockout mouse. female multiparous mice that carry the mmtv-deltan-beta-catenin transgene and that are heterozygous for p53 (tg(deltan-betacat)/+, p53+/-) display an in ... | 2006 | 16434961 |
| sustained trophism of the mammary gland is sufficient to accelerate and synchronize development of erbb2/neu-induced tumors. | epidemiological studies indicate that parity enhances her2/erbb2/neu-induced breast tumorigenesis. furthermore, recent studies using multiparous, erbb2/neu-overexpressing mouse mammary tumor virus (mmtv-neu) mice have shown that parity induces a population of cells that are targeted for erbb2/neu-induced transformation. although parity accelerates mammary tumorigenesis, the pattern of tumor development in multiparous mmtv-neu mice remains stochastic, suggesting that additional events are require ... | 2006 | 16434967 |
| functional characterization of the natural human glucocorticoid receptor (hgr) mutants hgralphar477h and hgralphag679s associated with generalized glucocorticoid resistance. | glucocorticoid resistance is often a result of mutations in the human glucocorticoid receptor alpha (hgralpha) gene, which impair one or more of hgralpha's functions. we investigated the molecular mechanisms through which two previously described mutant receptors, hgralphar477h and hgralphag679s, with amino acid substitutions in the dna- and ligand-binding domains, respectively, affect glucocorticoid signal transduction. | 2006 | 16449337 |
| prevalence of serologic reactivity against four strains of mouse mammary tumour virus among us women with breast cancer. | mouse mammary tumour virus (mmtv) causes breast cancer in mice, and mmtv-specific antibodies develop to high titers among mice infected as adults. whether mmtv or a related virus infects humans is uncertain, because mmtv dna sequences have been detected inconsistently and because serologic methods have varied widely. the current study used immunoblot and immunoprecipitation with four strains of mmtv (riii, fm, c3h, and la) to detect specific antibodies in 92 sera from us women with breast cancer ... | 2006 | 16449994 |
| an immune reaction may be necessary for cancer development. | background: the hypothesis of immunosurveillance suggests that new neoplasms arise very frequently, but most are destroyed almost at their inception by an immune response. its correctness has been debated for many years. in its support, it has been shown that the incidences of many tumor types, though apparently not all, tend to be increased in immunodeficient animals or humans, but this observation does not end the debate. alternative model: there is an alternative to the surveillance hypothesi ... | 2006 | 16457723 |
| transcriptional silencing of the mouse mammary tumor virus promoter through chromatin remodeling is concomitant with histone h1 phosphorylation and histone h3 hyperphosphorylation at m phase. | we examined histone phosphorylation and their effects on glucocorticoid receptor (gr)-mediated activation of the mouse mammary tumor virus promoter (mmtv) in synchronized cells. in vivo protein expression studies suggest that both histones h1 and h3 are highly phosphorylated in mitotic-arrested cells in which gr is unable to remodel chromatin and recruit transcription factor nf1 to the promoter. postmitotic cells show an open chromatin structure and efficient binding of nf1 to the promoter accom ... | 2006 | 16458342 |
| expression of a defective mouse mammary tumor virus envelope glycoprotein precursor which binds stably to grp78 within the lumen of the endoplasmic reticulum is associated with decreased glucocorticoid-induced apoptosis in mouse lymphoma cells. | viral proteins inhibit apoptosis in host cells by a variety of mechanisms. this report proposes an additional mechanism, based on the interaction of a mutant mouse mammary tumor virus (mmtv) envelope glycoprotein precursor, pr74, with the stress protein grp78 (bip) within the lumen of the endoplasmic reticulum (er) (j. biol. chem. 268 7482-7488, 1993). we show that wehi7.2 (w7.2) mouse lymphoma cells, which do not express pr74, are more sensitive to cell death induction by the glucocorticoid hor ... | 1997 | 16465242 |
| gene expression array analyses predict increased proto-oncogene expression in mmtv induced mammary tumors. | exogenous infection by milk-borne mouse mammary tumor viruses (mmtv) typically induce mouse mammary tumors in genetically susceptible mice at a rate of 90-95% by 1 year of age. in contrast to other transforming retroviruses, mmtv acts as an insertional mutagen and under the influence of steroid hormones induces oncogenic transformation after insertion into the host genome. as these events correspond with increases in adjacent proto-oncogene transcription, we used expression array profiling to de ... | 2006 | 16469401 |
| gradual elimination of retroviruses in ybr/ei mice. | mouse mammary tumor virus (mmtv), a well-characterized retrovirus that causes mammary tumors in susceptible mice, is commonly used to investigate virus-host interactions. we have shown that ybr/ei mice demonstrate a novel, dominant mechanism of resistance to mmtv infection and mmtv-induced mammary tumors. mmtv can both establish infection in ybr/ei mice and be transmitted by ybr/ei mice as an infectious virus. however, virus production is severely attenuated, resulting in gradual clearance of in ... | 2006 | 16474128 |
| identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection. | most enveloped viruses enter cells through binding of virion surface envelope proteins to receptors found on the plasma membrane of the cell. the beta retrovirus mouse mammary tumor virus (mmtv) uses transferrin receptor 1 (tfr1) to enter cells in a ph-dependent mechanism, probably co-trafficking with tfr1 to an acidic compartment where virus entry occurs. we have shown here that, although mouse and rat tfr1 function as entry receptors, cat, dog, hamster, or human tfr1s do not support mmtv infec ... | 2006 | 16481319 |
| wpre-mediated enhancement of gene expression is promoter and cell line specific. | the success of gene therapy approaches relies on sufficiently high levels of expression of the therapeutic gene. however, if tissue specific or tumour specific gene expression is desired, a lower level of transgene expression usually has to be accepted due to the weakness of the majority of available tissue or tumour specific promoters. this obstacle can in part be overcome by the insertion of viral cis-acting elements that enhance gene expression in various expression vector contexts regardless ... | 2006 | 16488559 |
| mammary tumorigenesis following transgenic expression of a dominant negative chk2 mutant. | a truncating allele of the cell cycle checkpoint kinase chk2 is present in 1% of the population, conferring a moderate increase in breast cancer risk, and inactivation of chk2 enhances mammary tumorigenesis in mice with targeted inactivation of brca1. we used the mouse mammary tumor virus (mmtv) promoter to target expression of a kinase-dead chk2 allele (d347a). mammary tumors, of predominantly micropapillary histology, developed in 40% of mmtv-chk2-d347a transgenic mice with an average latency ... | 2006 | 16488990 |
| overexpression of activated murine notch1 and notch3 in transgenic mice blocks mammary gland development and induces mammary tumors. | the mouse mammary tumor virus (mmtv) provirus was found to target the notch1 gene, producing insertional mutations in mammary tumors of mmtv/neu transgenic (tg) mice. in these mammary tumors, the notch1 gene is truncated upstream of the transmembrane domain, and the resulting notch1 intracellular domain (notch1(intra)), deleted of most extracellular sequences, is overexpressed. although notch1(intra) transforms mammary epithelial cells in vitro, its role in mammary gland tumor formation in vivo ... | 2006 | 16507912 |
| is mouse mammary tumor virus an etiologic agent of human breast cancer and lymphoma? | | 2006 | 16509544 |
| 7,12-dimethylbenz(a)anthracene treatment of a c-rel mouse mammary tumor cell line induces epithelial to mesenchymal transition via activation of nuclear factor-kappab. | the aberrant expression of the nuclear factor-kappab (nf-kappab) c-rel subunit that occurs in many human breast cancers can play a causal role in tumorigenesis as judged by findings with a mouse mammary tumor virus (mmtv)-c-rel transgenic mouse model, in which 31.6% of mice developed one or more mammary tumors after a long latency. interestingly, none of the cell lines established from the mammary tumors grew in soft agar. to begin to test the hypothesis that a prototypic carcinogen insult can p ... | 2006 | 16510574 |
| matrix metalloproteinases play an active role in wnt1-induced mammary tumorigenesis. | the wnt signaling transduction pathway plays a critical role in the pathogenesis of several murine and human epithelial cancers. here, we have used mouse mammary tumor virus (mmtv)-wnt1 transgenic mice, which develop spontaneous mammary adenocarcinoma, to examine whether matrix metalloproteinases (mmps)--a family of extracellular proteases implicated in multiple steps of cancer progression--contributed to wnt1-induced tumorigenesis. an analysis of the expression of several mmps by rt-pcr and in ... | 2006 | 16510589 |
| do dogs harbour risk factors for human breast cancer? | we ask consulting patients regularly whether they keep pets in order to identify zoonotic factors. it became apparent that patients with breast carcinoma (n=69) owned significantly more often dogs but not cats compared to age matched female controls. we compared the frequencies of dog and pet ownership with data from public available statistics on women (n=1320) of the same age group in bavaria. the most striking result was that more than twice the number of patients kept dogs permanently in the ... | 2006 | 16516398 |
| 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 |
| sequences within the gag gene of mouse mammary tumor virus needed for mammary gland cell transformation. | previously, we identified a group of replication-competent exogenous mouse mammary tumor viruses that failed to induce mammary tumors in susceptible mice. sequence comparison of tumorigenic and tumor-attenuated virus variants has linked the ability of virus to cause high-frequency mammary tumors to the gag gene. to determine the specific sequences within the gag gene that contribute to tumor induction, we constructed five distinct chimeric viruses that have various amino acid coding sequences of ... | 2006 | 16537589 |
| wnt-1 signal as a potential cancer therapeutic target. | wnt-1 was first identified as a proto-oncogene activated in mouse mammary tumors induced by mouse mammary tumor virus in 1982. wnt-1 signal is a secreted glycoprotein that plays important roles in embryonic development and carcinogenesis. in a conditional wnt-1 transgenic mouse tumor model, reduction of wnt-1 signaling results in the regression of the wnt-1 initiated primary mammary tumors and lung metastasis. aberrant activation of the wnt pathway has been strongly linked to the development of ... | 2006 | 16550254 |
| dominant negative retinoic acid receptor initiates tumor formation in mice. | retinoic acid suppresses cell growth and promotes cell differentiation, and pharmacological retinoic acid receptor (rar) activation is anti-tumorigenic. this begs the question of whether chronic physiological rar activation by endogenous retinoids is likewise anti-tumorigenic. | 2006 | 16563162 |
| distinct dna methylation activity of dnmt3a and dnmt3b towards naked and nucleosomal dna. | in mammals, the resetting of dna methylation patterns in early embryos and germ cells is crucial for development. de novo type dna methyltransferases dnmt3a and dnmt3b are responsible for creating dna methylation patterns during embryogenesis and in germ cells. although their in vitro dna methylation properties are similar, dnmt3a and dnmt3b methylate different genomic dna regions in vivo. in the present study, we have examined the dna methylation activity of dnmt3a and dnmt3b towards nucleosome ... | 2006 | 16567415 |
| 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 |
| hiv protease cleaves poly(a)-binding protein. | the pabp [poly(a)-binding protein] is able to interact with the 3' poly(a) tail of eukaryotic mrna, promoting its translation. cleavage of pabp by viral proteases encoded by several picornaviruses and caliciviruses plays a role in the abrogation of cellular protein synthesis. we report that infection of mt-2 cells with hiv-1 leads to efficient proteolysis of pabp. analysis of pabp integrity was carried out in bhk-21 (baby-hamster kidney) and cos-7 cells upon individual expression of the protease ... | 2006 | 16594896 |
| 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 |
| 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 |
| cleavage, a real turn-off? hiv-mediated proteolysis of pabp1. | in this issue of the biochemical journal, alvarez and colleagues have identified pabp1 [poly(a)-binding protein 1] as a target of protease cleavage during hiv infection. the study shows that hiv-1, hiv-2 and mouse mammary tumour virus, but not other retroviruses, target pabp1 for cleavage and identifies cleavage sites within the rna-recognition motifs and c-terminal region of the protein. this suggests that pabp1 cleavage may be important in the shut-off of host translation during hiv infection. ... | 2006 | 16703665 |
| 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 |
| 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 |
| 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 |
| development of real-time pcrs for detection and quantitation of human mmtv-like (hml) sequences hml expression in human tissues. | the human genome contains around 1000 betaretrovirus-like copies, human mouse mammary tumour virus (mmtv)-like (hml) groups 1-10, also referred to as human endogenous retrovirus "herv-k". despite many efforts, it is not established whether betaretroviruses, exo- or endogenous, are involved in the etiology of breast cancer, or other cancer diseases, in humans. quantitative real-time pcr (qpcr) taqman-based assays for hml groups 1-7, targeting the conserved reverse transcriptase (rt) and integrase ... | 2006 | 16713632 |
| 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 |
| control of phage bxb1 excision by a novel recombination directionality factor. | mycobacteriophage bxb1 integrates its dna at the attb site of the mycobacterium smegmatis genome using the viral attp site and a phage-encoded integrase generating the recombinant junctions attl and attr. the bxb1 integrase is a member of the serine recombinase family of site-specific recombination proteins and utilizes small (<50 base pair) substrates for recombination, promoting strand exchange without the necessity for complex higher order macromolecular architectures. to elucidate the regula ... | 2006 | 16719562 |
| 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 |
| 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 |