RT Journal Article SR Electronic T1 Down-regulation of Skp2 is Correlated with p27-associated Cell Cycle Arrest Induced by Phenylacetate in Human Prostate Cancer Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1881 OP 1888 VO 25 IS 3B A1 TAKUJI SHIBAHARA A1 TAKEHISA ONISHI A1 OMAR E. FRANCO A1 KIMINOBU ARIMA A1 YOSHIKI SUGIMURA YR 2005 UL http://ar.iiarjournals.org/content/25/3B/1881.abstract AB We have demonstrated that phenylacetate(PA)-induced cell cycle arrest in human prostate cancer is mediated by increase of p27. In this study, we further investigated the mechanism of PA-induced p27 expression in prostate cancer cells (LNCaP, androgen-independent LNCaP [AIDL] and PC-3). A striking decrease in Skp2 mRNA and protein expression and reciprocal increase in p27 protein level were observed in three PA-treated prostate cancer cells. Interestingly, reduction of phospho-Akt and up-regulation of p27 mRNA levels were observed only in PC-3 cells. No significant differences were found in phospho-Akt and p27 mRNA levels in LNCaP and AIDL. In vitro ubiquitination assay showed a decreased p27 ubquitination in PA-treated prostate cancer cells. Our results suggest that PA attenuated Skp2 expression, thereby inhibiting ubiquitination and promoting p27 accumulation in all three prostate cancer cell lines. Therapeutic strategies designed to reduce Skp2 may clinically play an important role in the treatment of both androgen-sensitive and hormone-refractory prostate cancer. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved