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Role of protein kinase C-iota in transformed non-malignant RWPE-1 cells and androgen-independent prostate carcinoma DU-145 cells.


ABSTRACT: UNLABELLED: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-iota) in androgen independent prostate DU-145 carcinoma cellscompared to transformed non-malignant prostate RWPE-1 cells. MATERIALS AND METHODS:Western blotting and immunoprecipitations demonstrated that PKC-iotaisassociated 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-iota silencing RNA (siRNA) decreased cell viability,cell-cycle accumulation at G2/M phase, and phosphorylation of Cdk7 and Cdk2. In addition, PKC-iota siRNA treatment caused less phosphorylation ofBad at ser-155, ser-136, and greater Bad/Bcl-xL 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 G1/S transition by accumulation of cells in G0/G1phase. 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-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.

SUBMITTER: Win HY 

PROVIDER: S-EPMC6496878 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Role of protein kinase C-iota in transformed non-malignant RWPE-1 cells and androgen-independent prostate carcinoma DU-145 cells.

Win H Y HY   Acevedo-Duncan M M  

Cell proliferation 20090401 2


<h4>Unlabelled</h4>Prostate cancer is one of the leading causes of death among men in the USA.<h4>Objective</h4>In this study, we investigated the role of atypical protein kinase C-iota (PKC-iota) in androgen independent prostate DU-145 carcinoma cellscompared to transformed non-malignant prostate RWPE-1 cells.<h4>Materials and methods</h4>Western blotting and immunoprecipitations demonstrated that PKC-iotaisassociated with cyclin-dependent kinase activating kinase (CAK/Cdk7) in RWPE-1 cells, bu  ...[more]

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