PURPOSE: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer. EXPERIMENTAL DESIGN: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. RESULTS: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis. CONCLUSIONS: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors.
PURPOSE: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer. EXPERIMENTAL DESIGN: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. RESULTS: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis. CONCLUSIONS: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors.
Authors: Joan P Breyer; Kate M McReynolds; Brian L Yaspan; Kevin M Bradley; William D Dupont; Jeffrey R Smith Journal: Cancer Epidemiol Biomarkers Prev Date: 2009-06-30 Impact factor: 4.254
Authors: Man-Li Luo; Chang Gong; Chun-Hau Chen; Daniel Y Lee; Hai Hu; Pengyu Huang; Yandan Yao; Wenjun Guo; Ferenc Reinhardt; Gerburg Wulf; Judy Lieberman; Xiao Zhen Zhou; Erwei Song; Kun Ping Lu Journal: Cancer Res Date: 2014-05-01 Impact factor: 12.701
Authors: Prudence B Lam; Laura N Burga; Bryan P Wu; Erin W Hofstatter; Kun Ping Lu; Gerburg M Wulf Journal: Mol Cancer Date: 2008-12-15 Impact factor: 27.401