Androgen receptor (AR), an androgen-activated transcription factor, belongs to the nuclear receptor superfamily. AR plays important role in the development and progression of prostate cancer (PCa). However, the role of AR in PCa metastasis is not fully understood. To investigate the role of androgen receptor (AR) in prostate cancer (PCa) metastasis, we examined AR expression level in primary and metastatic prostate cancer (PCa) by analyzing gene array data of 378 primary prostate tumors and 120 metastatic prostate tumors from Oncomine, as well as performed IHC staining of 56 prostate cancer samples. Expression of mRNA and protein of AR as well as its target gene prostate specific antigen (PSA) was much higher in metastatic prostate tumors. Knockdown of AR with siRNA or treating with anti-androgen Casodex reduced migration and invasion ability of C4-2B PCa cells. Knockdown of AR increased protein expression of E-cadherin and AR co-regulator KAT5 but reduced expression of epithelial-mesenchymal transition (EMT) marker proteins Slug, Snail, MMP-2, vimentin, and beta-catenin. Knockdown of KAT5 increased migration of C4-2B cells, while overexpression of KAT5 suppressed cell migration. KAT5 knockdown rescues the suppressive effect of AR knockdown on migration of C4-2B cell. Gene expression level of AR and KAT5 showed negative correlation. PCa patients with higher AR expression or lower KAT5 expression correlated to shorter recurrence-free survival. Our study suggested that elevation of AR expression and AR signaling in prostate tumors promotes PCa metastasis via induction of EMT and reduction of KAT5.
