Identification of a novel androgen receptor corepressor, CDC25A, in prostate cancer cells

Abstract

Androgen receptor (AR) is a ligand dependent transcription factor and its activity is regulated by numerous AR coregulators. Aberrant expression of AR coregulators in prostate cancer cells plays an important role in the development and progression of prostate cancer. We reported here that CDC25A, a cell cycle promoting phosphatase overexpressed in a number of cancers, functions as an AR coregulator suppressing the AR transcriptional activity. In this study, we found that CDC25A is upregulated in human prostate cancer cell lines when compared to the non-tumorigenic prostate epithelial cells. More importantly, we showed that CDC25A can physically interact with AR through its putative catalytic domain. In addition, ectopic expression of CDC25A in prostate cancer cell lines significantly suppresses PSA and probasin promoter activities, indicating that CDC25A may function as an AR corepressor. This was further confirmed by knockdown of CDC25A expression using siRNA, which resulted in upregulation of PSA promoter activity. Moreover, a truncated mutant that does not interact with AR fails to suppress the PSA promoter activity, indicating that CDC25A downregulates androgen responsive promoter by physically interact with AR. Taken together, our results demonstrated a novel function of CDC25A in the regulation of androgen signaling in human prostate cancer cells.