https://scholars.lib.ntu.edu.tw/handle/123456789/541990
標題: | CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells | 作者: | Chen M. Ni J. HONG-CHIANG CHANG Lin C.-Y. Muyan M. Yeh S. |
公開日期: | 2009 | 卷: | 30 | 期: | 5 | 起(迄)頁: | 841-850 | 來源出版物: | Carcinogenesis | 摘要: | Human prostate cancer (PCa) and prostate epithelial cells predominantly express estrogen receptor (ER) β, but not ERα. ERβ might utilize various ER coregulators to mediate the E2-signaling pathway in PCa. Here, we identified coiled-coil domain containing 62 (CCDC62)/ ERAP75 as a novel ER coactivator. CCDC62/ERAP75 is widely expressed in PCa cell lines and has low expression in MCF7 cells. Both in vitro and in vivo interaction assays using mammalian two-hybrid, glutathione S-transferase pull-down and coimmunoprecipitation methods proved that ERβ can interact with the C-terminus of CCDC62/ERAP75 via the ligand-binding domain. The first LXXLL motif within CCDC62/ERAP75 is required for the interaction between ERβ and CCDC62/ERAP75. Electrophoretic mobility shift assay showed that CCDC62/ERAP75 can be recruited by the estrogen response element-ER complex in the presence of ligand. Furthermore, a chromatin immunoprecipitation assay demonstrated the hormone-dependent recruitment of CCDC62/ERAP75 within the promoter of the estrogen-responsive gene cyclin D1. In addition, using silencing RNA (siRNA) against endogeneous CCDC62/ERAP75, we demonstrated that inhibition of endogenous CCDC62/ERAP75 results in the suppression of ERβ-mediated transactivation as well as target gene expression in LNCaP cells. More importantly, using the tet-on overexpression system, we showed that induced expression of CCDC62/ERAP75 can enhance the E2-regulated cyclin D1 expression and cell growth in LNCaP cells. Together, our results revealed the role of CCDC62/ERAP75 as a novel coactivator in PCa cells that can modulate ERβ transactivation and receptor function. ? The Author 2009. Published by Oxford University Press. All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-65549162723&doi=10.1093%2fcarcin%2fbgn288&partnerID=40&md5=9e814a056e8def758eba4472e2c82abd https://scholars.lib.ntu.edu.tw/handle/123456789/541990 |
ISSN: | 0143-3334 | DOI: | 10.1093/carcin/bgn288 | SDG/關鍵字: | binding protein; coiled coil domain containing 62 protein; cyclin D1; estrogen receptor beta; unclassified drug; article; carboxy terminal sequence; cell growth; cell strain LNCaP; cell strain MCF 7; chromatin immunoprecipitation; controlled study; estrogen responsive element; gel mobility shift assay; gene expression; hormone dependence; human; human cell; ligand binding; priority journal; prostate cancer; protein protein interaction; transactivation; Animals; Cell Division; Cell Line, Tumor; Cloning, Molecular; Estrogen Receptor beta; Gene Expression Regulation, Neoplastic; Humans; Male; Mice; Polymerase Chain Reaction; Prostatic Neoplasms; Receptors, Estrogen; RNA Interference; Signal Transduction; Testis; Transcription Factors; Transcriptional Activation |
顯示於: | 醫學系 |
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