Activation of β-Catenin Signaling in Prostate Cancer by Peptidyl-Prolyl Isomerase Pin1-Mediated Abrogation of the Androgen Receptor-β-Catenin Interaction

• DOI: 10.1128/mcb.26.3.929-939.2006
• Publication Date: 2006-01-20T17:28:11Z
• Authors: Shao-Yong Chen; Gerburg Wulf; Xiao Zhen Zhou; Mark A. Rubin; Kun Ping Lu; Steven P. Balk
• Keywords: Beta-catenin; TCF4; GSK3B

Androgen receptor (AR) interacts with ␤-catenin and can suppress its coactivation of T cell factor 4 (Tcf4) in prostate cancer (PCa) cells.Pin1 is a peptidyl-prolyl cis/trans isomerase that stabilizes by inhibiting binding to the adenomatous polyposis coli gene product subsequent glycogen synthase kinase 3␤ (GSK-3␤)-dependent degradation.Higher Pin1 expression primary PCa correlated disease recurrence, this study found was markedly increased metastatic PCa.Consistent result, transfected LNCaP cells strongly accelerated tumor growth vivo immunodeficient mice.Pin1 enhanced ␤-catenin/Tcf4 transcriptional activity, as assessed using Tcf4-regulated reporter genes, endogenous Tcf4 c-myc.However, contrast results intact PTEN active GSK-3␤, cells, which are deficient, did not increase ␤-catenin.Instead, inhibited interaction AR, abrogated ability AR antagonize activity.These findings demonstrate signaling, AR-␤-catenin be regulated Pin1, abrogation enhance signaling contribute aggressive biological behavior PCa.