title: Inability of NCoR/SMRT to repress androgen receptor transcriptional activity in prostate cancer cell lines.
abstract: The molecular mechanisms leading to castration-resistant prostate cancer (CRPC) are poorly understood. Among several mechanisms leading to CRPC growth a dysregulation of androgen receptor (AR) co-regulators (i.e. up-regulation of co-activators or down-regulation of co-repressors) is discussed. There are numerous reports demonstrating an increased expression of co-activators during prostate cancer progression. On the contrary, the impact of co-repressors on tumor growth and development is less clear. In this study we compared the effects of two known co-repressors, NCoR and SMRT, on AR transcriptional activity in prostate cancer (PCa) cell lines and compared them to that in COS-1 cells. Interestingly, we found that NCoR/SMRT overexpression did not repress AR-dependent gene expression in the PCa cell lines, but rather activated it. This finding is probably due to an impaired AR-co-repressor interaction in the prostate cancer cell lines. In conclusion, we provide evidence that up-regulation of NCoR or SMRT may increase transcriptional activity of the AR in a cell type-specific context.
authors: Institute of General Zoology and Endocrinology, Ulm University, Albert-Einstein-Allee 11, D-89069 Ulm, Germany. martin.laschak@uni-ulm.de
authors: Martin
authors: M
authors: Laschak
authors: Marina
authors: M
authors: Bechtel
authors: Klaus-Dieter
authors: KD
authors: Spindler
authors: Andrea
authors: A
authors: Hessenauer
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D056985:Nuclear Receptor Co-Repressor 2 / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*
chemical_list: D056985:Nuclear Receptor Co-Repressor 2; D011944:Receptors, Androgen