期刊
CELL PROLIFERATION
卷 42, 期 2, 页码 182-194出版社
WILEY
DOI: 10.1111/j.1365-2184.2009.00582.x
关键词
-
类别
资金
- Inhibiton Therapeutics Inc.,
- Sapphire Foundation
- Research Service of the Veterans' Administration
Prostate cancer is one of the leading causes of death among men in the USA. In this study, we investigated the role of atypical protein kinase C-iota (PKC-iota) in androgen-independent prostate DU-145 carcinoma cells compared to transformed non-malignant prostate RWPE-1 cells. Western blotting and immunoprecipitations demonstrated that PKC-iota is associated with cyclin-dependent kinase activating kinase (CAK/Cdk7) in RWPE-1 cells, but not in DU-145 cells. Treatment of prostate RWPE-1 cells with PKC-iota silencing RNA (siRNA) decreased cell viability, cell-cycle accumulation at G(2)/M phase, and phosphorylation of Cdk7 and Cdk2. In addition, PKC-iota siRNA treatment caused less phosphorylation of Bad at ser-155, ser-136, and greater Bad/Bcl-x(L) heterodimerization, leading to apoptosis. In DU-145 cells, PKC-iota was anti-apoptotic and was required for cell survival. Treatment with PKC-iota siRNA blocked increase in cell number, and inhibited G(1)/S transition by accumulation of cells in G(0)/G(1) 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. Our results suggest that PKC-iota 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-iota lead to apoptosis in DU-145 prostate cells.
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