Decreased BRCA1 confers tamoxifen resistance in breast cancer cells by altering estrogen receptor-coregulator interactions.


:The breast cancer susceptibility gene 1 (BRCA1) is mutated in approximately 50% of hereditary breast cancers, and its expression is decreased in 30-40% of sporadic breast cancers, suggesting a general role in breast cancer development. BRCA1 physically and functionally interacts with estrogen receptor-alpha (ERalpha) and several transcriptional regulators. We investigated the relationship between cellular BRCA1 levels and tamoxifen sensitivity. Decreasing BRCA1 expression in breast cancer cells by small interfering RNA alleviated tamoxifen-mediated growth inhibition and abolished tamoxifen suppression of several endogenous ER-targeted genes. ER-stimulated transcription and cytoplasmic signaling was increased without detectable changes in ER or ER coregulator expression. Co-immunoprecipitation studies showed that with BRCA1 knockdown, tamoxifen-bound ERalpha was inappropriately associated with coactivators, and not effectively with corepressors. Chromatin immunoprecipitation studies demonstrated that with tamoxifen, BRCA1 knockdown did not change ERalpha promoter occupancy, but resulted in increased coactivator and decreased corepressor recruitment onto the endogenous cyclin D1 promoter. Our results suggest that decreased BRCA1 levels modify ERalpha-mediated transcription and regulation of cell proliferation in part by altering ERalpha-coregulator association. In the presence of tamoxifen, decreased BRCA1 expression results in increased coactivator and decreased corepressor recruitment on ER-regulated gene promoters.






Wen J,Li R,Lu Y,Shupnik MA




Has Abstract


2009-01-29 00:00:00
















  • Mitochondrial DNA mutations in human cancer.

    abstract::Somatic mitochondrial DNA (mtDNA) mutations have been increasingly observed in primary human cancers. As each cell contains many mitochondria with multiple copies of mtDNA, it is possible that wild-type and mutant mtDNA can co-exist in a state called heteroplasmy. During cell division, mitochondria are randomly distri...


    pub_type: 杂志文章,评审


    authors: Chatterjee A,Mambo E,Sidransky D

    更新日期:2006-08-07 00:00:00

  • A novel conditional NPM-ALK-driven model of CD30+ T-cell lymphoma mediated by a translational stop cassette.

    abstract::Targeted expression of transgenes is essential for the accurate representation of human disease in in vivo models. Current approaches to generate conditional transgenic mouse models are cumbersome and not amenable to high-throughput analysis since they require de novo generation and characterization of genetically mod...


    pub_type: 杂志文章


    authors: Shoumariyeh K,Schneider N,Poggio T,Veratti P,Ehrenfeld S,Redhaber DM,Khan R,Pfeifer D,Klingeberg C,Kreutmair S,Rudelius M,Quintanilla-Martinez L,Fend F,Illert AL,Duyster J,Miething C

    更新日期:2020-02-01 00:00:00

  • MKP1/CL100 controls tumor growth and sensitivity to cisplatin in non-small-cell lung cancer.

    abstract::Non-small-cell lung cancer (NSCLC) represents the most frequent and therapy-refractive sub-class of lung cancer. Improving apoptosis induction in NSCLC represents a logical way forward in treating this tumor. Cisplatin, a commonly used therapeutic agent in NSCLC, induces activation of N-terminal-c-Jun kinase (JNK) tha...


    pub_type: 杂志文章


    authors: Chattopadhyay S,Machado-Pinilla R,Manguan-García C,Belda-Iniesta C,Moratilla C,Cejas P,Fresno-Vara JA,de Castro-Carpeño J,Casado E,Nistal M,Gonzalez-Barón M,Perona R

    更新日期:2006-06-01 00:00:00

  • p8-deficient fibroblasts grow more rapidly and are more resistant to adriamycin-induced apoptosis.

    abstract::p8 is a stress-induced DNA-binding protein, biochemically related to the architectural chromatin binding HMG protein family and whose function is presently unknown. We obtained fibroblast from mice lacking p8 and found that p8 is involved in cell growth regulation and in apoptosis. p8(-/-) mouse embryonic fibroblasts ...


    pub_type: 杂志文章


    authors: Vasseur S,Hoffmeister A,Garcia-Montero A,Mallo GV,Feil R,Kühbandner S,Dagorn JC,Iovanna JL

    更新日期:2002-03-07 00:00:00

  • Cyclin D3 action in androgen receptor regulation and prostate cancer.

    abstract::Prostate cancer (PCa) cell proliferation is dependent on activation of the androgen receptor (AR), a ligand-dependent transcription factor. AR activation controls G1-S phase progression through fostering enhanced translation of the D-type cyclins, which promote cell cycle progression through activation of CDK4/6. Howe...


    pub_type: 杂志文章


    authors: Olshavsky NA,Groh EM,Comstock CE,Morey LM,Wang Y,Revelo MP,Burd C,Meller J,Knudsen KE

    更新日期:2008-05-15 00:00:00

  • Post-transcriptional processing suggests that c-mos functions as a maternal message in mouse eggs.

    abstract::Transcripts of the c-mos proto-oncogene were recently found to accumulate to high levels in mouse oocytes. We report here that the oocyte c-mos RNA is polyadenylated in concert with oocyte maturation, retained in mature ovulated eggs and zygotes but degraded by the late two cell embryo stage. These results suggest tha...


    pub_type: 杂志文章


    authors: Goldman DS,Kiessling AA,Cooper GM

    更新日期:1988-08-01 00:00:00

  • Enhanced EGF mitogenic response is associated with enhanced tyrosine phosphorylation of specific cellular proteins in fibroblasts overexpressing c-src.

    abstract::In previous studies examining the role of pp60c-src in cellular proliferation, we demonstrated that overexpression of wild type (wt) but not mutated c-src in C3H10T1/2 murine embryo fibroblasts resulted in a 2 to 5 fold enhancement of DNA synthesis in response to epidermal growth factor (EGF). Using phosphotyrosine an...


    pub_type: 杂志文章


    authors: Wilson LK,Parsons SJ

    更新日期:1990-10-01 00:00:00

  • Retinoid-dependent antagonism of serum response factor transactivation mediated by transcriptional coactivator proteins.

    abstract::Transcriptional coactivators SRC-1 and p300 specifically interact with liganded-nuclear receptors and also modulate other transcription factors, including serum response factor (SRF). Here, we report that retinoids repress transactivation by SRF and specific interactions exist between the DNA binding domains of SRF an...


    pub_type: 杂志文章


    authors: Kim SW,Kim HJ,Jung DJ,Lee SK,Kim YS,Kim JH,Kim TS,Lee JW

    更新日期:2001-10-04 00:00:00

  • Oncogenic Y641 mutations in EZH2 prevent Jak2/β-TrCP-mediated degradation.

    abstract::EZH2 (enhancer of zeste homolog 2) is a critical enzymatic subunit of the polycomb repressive complex 2 (PRC2), which trimethylates histone H3 (H3K27) to mediate gene repression. Somatic mutations, overexpression and hyperactivation of EZH2 have been implicated in the pathogenesis of several forms of cancer. In partic...


    pub_type: 杂志文章


    authors: Sahasrabuddhe AA,Chen X,Chung F,Velusamy T,Lim MS,Elenitoba-Johnson KS

    更新日期:2015-01-22 00:00:00

  • Rho GTPases: Anti- or pro-neoplastic targets?

    abstract::Rho GTPases are critical signal transducers of multiple pathways. They have been proposed to be useful anti-neoplastic targets for over two decades, especially in Ras-driven cancers. Until recently, however, few in vivo studies had been carried out to test this premise. Several recent mouse model studies have verified...


    pub_type: 杂志文章,评审


    authors: Zandvakili I,Lin Y,Morris JC,Zheng Y

    更新日期:2017-06-08 00:00:00

  • Different functions are required for initiation and maintenance of immortalization of rat embryo fibroblasts by SV40 large T antigen.

    abstract::We have used two different, but complementary assays to characterize functions of SV40 T antigen that are necessary for its ability to immortalize rat embryo fibroblasts. In accordance with previous work, we found that several functions were required. These include activities that map to the p53 binding domain and the...


    pub_type: 杂志文章


    authors: Powell AJ,Darmon AJ,Gonos ES,Lam EW,Peden KW,Jat PS

    更新日期:1999-12-02 00:00:00

  • Involvement of programmed cell death 4 in transforming growth factor-beta1-induced apoptosis in human hepatocellular carcinoma.

    abstract::The programmed cell death 4 (PDCD4) gene was originally identified as a tumor-related gene in humans and acts as a tumor-suppressor in mouse epidermal carcinoma cells. However, its function and regulatory mechanisms of expression in human cancer remain to be elucidated. We therefore investigated the expression of PDCD...


    pub_type: 杂志文章


    authors: Zhang H,Ozaki I,Mizuta T,Hamajima H,Yasutake T,Eguchi Y,Ideguchi H,Yamamoto K,Matsuhashi S

    更新日期:2006-10-05 00:00:00

  • Regulation of the bi-directional cross-talk between ovarian cancer cells and adipocytes by SPARC.

    abstract::Ovarian cancer (OvCa) exhibits a specific predilection for metastasis to the omentum. Our earlier studies highlighted the tumour-suppressor effect of secreted protein acidic and rich in cysteine (SPARC) in OvCa through multi-faceted roles inhibiting cancer cell interactions within the peritoneal milieu. The goal of th...


    pub_type: 杂志文章


    authors: John B,Naczki C,Patel C,Ghoneum A,Qasem S,Salih Z,Said N

    更新日期:2019-05-01 00:00:00

  • Molecular mechanisms of constitutive NF-kappaB/Rel activation in Hodgkin/Reed-Sternberg cells.

    abstract::A common characteristic of malignant cells derived from patients with Hodgkin's disease (HD) is a high level of constitutive nuclear NF-kappaB/Rel activity, which stimulates proliferation and confers resistance to apoptosis. We have analysed the mechanisms that account for NF-kappaB activation in a panel of Hodgkin/Re...


    pub_type: 杂志文章


    authors: Krappmann D,Emmerich F,Kordes U,Scharschmidt E,Dörken B,Scheidereit C

    更新日期:1999-01-28 00:00:00

  • The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms.

    abstract::The whey acidic protein (WAP) domain is a conserved motif, containing eight cysteines found in a characteristic 4-disulphide core arrangement, that is present in a number of otherwise unrelated proteins. WAP motifs are present in SLPI and elafin, two antiproteinases located on chromosome 20q12-13, in a locus rich in p...


    pub_type: 杂志文章


    authors: Bingle L,Singleton V,Bingle CD

    更新日期:2002-04-18 00:00:00

  • Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice.

    abstract::The von Hippel-Lindau tumor suppressor pVHL regulates the stability of hypoxia-inducible factors (HIF)-1 and -2, oxygen-sensitive basic helix-loop-helix transcription factors, which mediate the hypoxic induction of angiogenic growth factors such as vascular endothelial growth factor. Loss of pVHL function results in c...


    pub_type: 杂志文章


    authors: Rankin EB,Rha J,Unger TL,Wu CH,Shutt HP,Johnson RS,Simon MC,Keith B,Haase VH

    更新日期:2008-09-11 00:00:00

  • The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene.

    abstract::Overexpression of HER-2/neu (also known as c-erbB-2) proto-oncogene frequently occurs in many different types of human cancers, including ovarian carcinoma, and is known to enhance tumor metastasis and chemoresistance. Previous studies showed that inhibition of HER-2/neu expression by various agents, such as adenoviru...


    pub_type: 杂志文章


    authors: Lin YC,Peng JM,Wang WB

    更新日期:2000-05-18 00:00:00

  • Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer.

    abstract::Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with...


    pub_type: 杂志文章


    authors: Funakoshi T,Tachibana I,Hoshida Y,Kimura H,Takeda Y,Kijima T,Nishino K,Goto H,Yoneda T,Kumagai T,Osaki T,Hayashi S,Aozasa K,Kawase I

    更新日期:2003-02-06 00:00:00

  • p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia.

    abstract::The retinoblastoma gene product (pRb) controls proliferation and differentiation processes in stratified epithelia. Importantly, and in contrast to other tissues, Rb deficiency does not lead to spontaneous skin tumor formation. As the cyclin-dependent kinase inhibitor p21 regulates proliferation and differentiation in...


    pub_type: 杂志文章


    authors: Saiz-Ladera C,Lara MF,Garín M,Ruiz S,Santos M,Lorz C,García-Escudero R,Martínez-Fernández M,Bravo A,Fernández-Capetillo O,Segrelles C,Paramio JM

    更新日期:2014-09-11 00:00:00

  • PMP24, a gene identified by MSRF, undergoes DNA hypermethylation-associated gene silencing during cancer progression in an LNCaP model.

    abstract::Transcriptional silencing of antitumor genes via CpG island methylation could be a mechanism mediating prostate cancer (PCa) progression from an androgen-sensitive (AS) to an androgen-insensitive (AI) state. We have used the methylation-sensitive restriction fingerprinting (MSRF) technique to identify novel CpG-rich s...


    pub_type: 杂志文章


    authors: Wu M,Ho SM

    更新日期:2004-01-08 00:00:00

  • Activation of p53 by roscovitine-mediated suppression of MDM2 expression.

    abstract::The p53 tumor suppressor is regulated by the MDM2 oncoprotein. Overexpression of MDM2 maintains p53 at low levels and contributes to the functional inactivation of p53 in a subset of tumors. We found that treatment with roscovitine and olomoucin, which were originally developed as cyclin-dependent kinase (CDK) inhibit...


    pub_type: 杂志文章


    authors: Lu W,Chen L,Peng Y,Chen J

    更新日期:2001-05-31 00:00:00

  • CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development.

    abstract::Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT com...


    pub_type: 杂志文章


    authors: Shirai YT,Mizutani A,Nishijima S,Horie M,Kikuguchi C,Elisseeva O,Yamamoto T

    更新日期:2019-04-01 00:00:00

  • Overexpression of the thymosin beta-4 gene is associated with malignant progression of SW480 colon cancer cells.

    abstract::Thymosin beta-4 (Tbeta-4), a small peptide originally isolated from calf thymus, modulates the formation of F-actin microfilaments by sequestering the monomeric G-actin. Recent studies have shown that overexpression of the Tbeta-4 gene occurs not only in many human carcinomas but also in the highly metastatic melanoma...


    pub_type: 杂志文章


    authors: Wang WS,Chen PM,Hsiao HL,Ju SY,Su Y

    更新日期:2003-05-22 00:00:00

  • Unmasking by soluble IL-6 receptor of IL-6 effect on metastatic melanoma: growth inhibition and differentiation of B16-F10.9 tumor cells.

    abstract::Interleukin-6 (IL-6) inhibits the growth of melanocytes and of early stage melanoma cells, but not that of advanced melanoma cells. The in vitro IL-6 response can be restored in the highly metastatic melanoma B16-F10.9 by addition of recombinant soluble IL-6 receptor alpha-chain (sIL-6R). The F10.9 cells then undergo ...


    pub_type: 杂志文章


    authors: Oh JW,Katz A,Harroch S,Eisenbach L,Revel M,Chebath J

    更新日期:1997-07-31 00:00:00

  • Melanoma metastasis: new concepts and evolving paradigms.

    abstract::Melanoma progression is typically depicted as a linear and stepwise process in which metastasis occurs relatively late in disease progression. Significant evidence suggests that in a subset of melanomas, progression is much more complex and less linear in nature. Epidemiologic and experimental observations in melanoma...


    pub_type: 杂志文章,评审


    authors: Damsky WE,Theodosakis N,Bosenberg M

    更新日期:2014-05-08 00:00:00

  • Differential SKIP expression in PTEN-deficient glioblastoma regulates cellular proliferation and migration.

    abstract::Glioblastoma is the most common and lethal primary malignant brain tumor in adults. The tumor suppressor gene PTEN is deleted, mutated or hypermethylated in more than 60% of glioblastoma cases resulting in hyperactivation of the phosphoinositide 3-kinase pathway, which leads to sustained PI(3,4,5)P3 signaling, and the...


    pub_type: 杂志文章


    authors: Davies EM,Kong AM,Tan A,Gurung R,Sriratana A,Bukczynska PE,Ooms LM,McLean CA,Tiganis T,Mitchell CA

    更新日期:2015-07-01 00:00:00

  • Transcriptional activation of the hepatocyte growth factor receptor (c-met) gene by its ligand (hepatocyte growth factor) is mediated through AP-1.

    abstract::Hepatocyte Growth Factor (HGF) exerts its biological effects via binding and activating a transmembrane protein tyrosine kinase receptor known as c-Met. Previous studies from our laboratory demonstrated that c-met gene expression is inducible by its own ligand (HGF). However, the molecular mechanism(s) involved in thi...


    pub_type: 杂志文章


    authors: Seol DW,Chen Q,Zarnegar R

    更新日期:2000-02-24 00:00:00

  • Discovery of differentially expressed genes in human breast cancer using subtracted cDNA libraries and cDNA microarrays.

    abstract::Identifying novel and known genes that are differentially expressed in breast cancer has important implications in understanding the biology of breast tumorigenesis and developing new diagnostic and therapeutic agents. In this study we have combined two powerful technologies, PCR-based cDNA subtraction and cDNA microa...


    pub_type: 杂志文章


    authors: Jiang Y,Harlocker SL,Molesh DA,Dillon DC,Stolk JA,Houghton RL,Repasky EA,Badaro R,Reed SG,Xu J

    更新日期:2002-03-28 00:00:00

  • An FGFR inhibitor converts the tumor promoting effect of TGF-β by the induction of fibroblast-associated genes of hepatoma cells.

    abstract::Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formati...


    pub_type: 杂志文章


    authors: Zhang HR,Wang XD,Yang X,Chen D,Hao J,Cao R,Wu XZ

    更新日期:2017-07-06 00:00:00

  • Shp2 promotes metastasis of prostate cancer by attenuating the PAR3/PAR6/aPKC polarity protein complex and enhancing epithelial-to-mesenchymal transition.

    abstract::Epithelial-to-mesenchymal transition (EMT), marked by the dissolution of cell-cell junctions, loss of cell polarity and increased cell motility, is one of the essential steps for prostate cancer metastasis. However, the underlying mechanism has not been fully explored. We report in this study that Shp2 is upregulated ...


    pub_type: 杂志文章


    authors: Zhang K,Zhao H,Ji Z,Zhang C,Zhou P,Wang L,Chen Q,Wang J,Zhang P,Chen Z,Zhu HH,Gao WQ

    更新日期:2016-03-10 00:00:00