Role of protein kinase C-iota in transformed non-malignant RWPE-1 cells and androgen-independent prostate carcinoma DU-145 cells |
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Authors: | H Y Win M Acevedo-Duncan† |
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Institution: | Department of Chemistry, University of South Florida, and;James A. Haley Veteran Hospital, Tampa, Florida, USA |
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Abstract: | Prostate cancer is one of the leading causes of death among men in the USA. Objective: In this study, we investigated the role of atypical protein kinase C-iota (PKC-ι) in androgen-independent prostate DU-145 carcinoma cells compared to transformed non-malignant prostate RWPE-1 cells. Materials and methods: Western blotting and immunoprecipitations demonstrated that PKC-ι is associated with cyclin-dependent kinase activating kinase (CAK/Cdk7) in RWPE-1 cells, but not in DU-145 cells. Results: Treatment of prostate RWPE-1 cells with PKC-ι silencing RNA (siRNA) decreased cell viability, cell-cycle accumulation at G2/M phase, and phosphorylation of Cdk7 and Cdk2. In addition, PKC-ι siRNA treatment caused less phosphorylation of Bad at ser-155, ser-136, and greater Bad/Bcl-xL heterodimerization, leading to apoptosis. In DU-145 cells, PKC-ι was anti-apoptotic and was required for cell survival. Treatment with PKC-ι siRNA blocked increase in cell number, and inhibited G1/S transition by accumulation of cells in G0/G1 phase. In addition to cell-cycle arrest, both RWPE-1 and DU-145 cells underwent apoptosis due to mitochondrial dysfunction and apoptosis cascades, such as release of cytochrome c, activation of caspase-7, and poly (ADP-ribose) polymerase (PARP) cleavage. Conclusion: Our results suggest that PKC-ι is required for cell survival in both transformed non-malignant prostate RWPE-1 cells and androgen-independent malignant prostate DU-145 cells, whereas suppressing PKC-ι lead to apoptosis in DU-145 prostate cells. |
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