Regulation of AR and (beta)-Catenin Signaling by Pin 1 in Prostate Cancer

摘要

One part of the Final report was included in the attached Manuscript, demonstrating a positive role of Pin1 in PCa progression. The mechanisms include that Pin1 can enhance beta-catenin nuclear localization, TCF/beta- catenin dependent Topflash activity, and c-Myc and Cyclin D1 expression, and disrupt AR-mediated suppression of TCF/beta-catenin signaling. We provided additional data suggesting Pin1 reduces AR transcriptional activity and PSA expression, mediated by repression of the N-C interaction. We also showed that in androgen-independent PCa C4 cells pin1 is overexpressed and overexpression of Pin1 in LNCaP cells leads to increased invasiveness. We confirmed the Pin1 is involved in the G2-M checkpoint in PCa cells, however its connection to PCa development is unclear. Another finding is that APC is expressed mainly in LNCaP nucleus and our preliminary results showed reduction of APC expression in LNCaP and PC3 cells leads to enhanced beta-catenin/Tcf4 activity.