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PKC? activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells.


ABSTRACT: BACKGROUND:PKC? is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells. METHODS:Here, we investigated the role of PKC? on the growth of PC-3 human prostate cancer cells in vivo and in vitro. RESULTS:We found that sustained treatment with a specific PKC? activator (?? receptor for active C kinase, ??RACK) increased growth of PC-3 xenografts. There was increased levels of HIF-1?, vascular endothelial growth factor and CD31-positive cells in PC-3 xenografts, representative of increased tumor angiogenesis. Mechanistically, PKC? activation increased the levels of reactive oxygen species (ROS) by binding to and phosphorylating NADPH oxidase, which induced its activity. Also, PKC?-induced activation of NADPH oxidase increased the level of HIF-1?. CONCLUSIONS:Our results using tumors from the PC-3 xenograft model suggest that PKC? activation increases angiogenic activity in androgen-independent PC-3 prostate cancer cells by increasing NADPH oxidase activity and HIF-1? levels and thus may partly be responsible for increased angiogenesis in advanced prostate cancer.

SUBMITTER: Kim J 

PROVIDER: S-EPMC3544470 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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PKCδ activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells.

Kim Jeewon J   Koyanagi Tomoyoshi T   Mochly-Rosen Daria D  

The Prostate 20101123 9


<h4>Background</h4>PKCδ is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells.<h4>Methods</h4>Here, we investigated the role of PKCδ on the growth of PC-3 human prostate cancer cells in vivo and in vitro.<h4>Results</h4>We found that sustained treatment with a specific PKCδ activator (ψδ receptor for active C kinase, ψδRACK) increased growth of PC-3 xenografts. There was increased levels of HIF-1α, vascular endothelial growth factor and CD31-positive  ...[more]

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