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: Martin Laschak, Marina Bechtel, Klaus-Dieter Spindler, Andrea Hessenauer
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 28 Issue 4 Pg. 645-51 (Oct 2011) ISSN: 1791-244X [Electronic] Greece
• PMID: 21720703 (Publication Type: Journal Article)

Chemical References

• Nuclear Receptor Co-Repressor 2
• Receptors, Androgen

Topics

• Animals
• Blotting, Western
• COS Cells
• Cell Line, Tumor
• Chlorocebus aethiops
• Humans
• Male
• Nuclear Receptor Co-Repressor 2 (genetics, metabolism)
• Prostatic Neoplasms (metabolism)
• Receptors, Androgen (genetics, metabolism)