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 has an important role in the development and progression of
prostate cancer. We report here that CDC25A, a cell cycle-promoting
phosphatase over-expressed 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 and its expression level is positively associated with the Gleason score and disease
metastasis. 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 suppresses PSA and
Probasin promoter activities significantly, indicating that CDC25A may function as an AR
corepressor. This was further confirmed by knockdown of endogenous CDC25A expression using
small interfering RNA (
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 interacting with AR. Taken together, our results demonstrated a novel function of CDC25A in the regulation of
androgen signaling in human
prostate cancer cells.