Background: Androgen receptor (AR) plays critical roles in both androgen-dependent and androgen-independent prostatecancer. In prostate cancer, alterations in the p53 gene are clearly associated with progressive disease and there is increasingevidence that p53 may directly regulate androgen signaling. Nevertheless, the coactivator functional role of Zac1(zinc-fi nger protein which regulates apoptosis and cell cycle arrest 1), its human ortholog ZAC1, a strong coactivator forAR and p53, remains unclear in human prostate cancer cell lines. Methods: The expression levels of AR, p53, and ZAC1proteins and the effects of various reagents in human prostate cancer cell lines were examined by Western blot analysis.The functional status of AR and p53 were examined via Zac1 by the reporter system of androgen-responsive-element andp53-responsive-element promoters, respectively. Results: We demonstrate relationships between AR and p53 protein levels,including the negative effect of p53 on AR expression and the up-regulation of p21WAF1/CIP1 protein expression by ARand p53. By using luciferase reporter systems together with Zac1, a strong coactivator for AR and p53, our data indicatethat the p53 protein is functional in three human prostate cancer cell lines tested, namely LNCaP, DU-145 and PC-3 cells,while the AR protein is functional only in LNCaP cells. Conclusions: Our fi ndings evidence that there is a fi ne balancebetween AR and p53 protein levels, and their functional roles in cells may depend on their post-translational modifi cationsand the relative amounts of ZAC1 in human prostate cancer cells.