CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells.
| dc.contributor.author | Chen, Ming | |
| dc.contributor.author | Ni, Jing | |
| dc.contributor.author | Chang, Hong-Chiang | |
| dc.contributor.author | Lin, Chen-Yong | |
| dc.contributor.author | Muyan, Mesut | |
| dc.contributor.author | Yeh, Shuyuan | |
| dc.date.accessioned | 2020-12-12T02:46:43Z | |
| dc.date.available | 2020-12-12T02:46:43Z | |
| dc.date.issued | 2009-05 | |
| dc.date.updated | 2020-12-12T02:46:41Z | |
| dc.description.abstract | Human prostate cancer (PCa) and prostate epithelial cells predominantly express estrogen receptor (ER) beta, but not ERalpha. ERbeta 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 ERbeta 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 ERbeta 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 ERbeta-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 ERbeta transactivation and receptor function. | |
| dc.identifier | bgn288 | |
| dc.identifier.issn | 0143-3334 | |
| dc.identifier.issn | 1460-2180 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Oxford University Press (OUP) | |
| dc.relation.ispartof | Carcinogenesis | |
| dc.relation.isversionof | 10.1093/carcin/bgn288 | |
| dc.subject | Testis | |
| dc.subject | Cell Line, Tumor | |
| dc.subject | Animals | |
| dc.subject | Humans | |
| dc.subject | Mice | |
| dc.subject | Prostatic Neoplasms | |
| dc.subject | Receptors, Estrogen | |
| dc.subject | Estrogen Receptor beta | |
| dc.subject | Transcription Factors | |
| dc.subject | Cloning, Molecular | |
| dc.subject | Polymerase Chain Reaction | |
| dc.subject | Signal Transduction | |
| dc.subject | Cell Division | |
| dc.subject | Gene Expression Regulation, Neoplastic | |
| dc.subject | RNA Interference | |
| dc.subject | Male | |
| dc.subject | Transcriptional Activation | |
| dc.title | CCDC62/ERAP75 functions as a coactivator to enhance estrogen receptor beta-mediated transactivation and target gene expression in prostate cancer cells. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Chen, Ming|0000-0002-3470-1062 | |
| pubs.begin-page | 841 | |
| pubs.end-page | 850 | |
| pubs.issue | 5 | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Duke Cancer Institute | |
| pubs.organisational-group | Pathology | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Institutes and Centers | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.publication-status | Published | |
| pubs.volume | 30 |