BACKGROUND: PKCδ is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells. METHODS: Here, we investigated the role of PKCδ on the growth of PC-3 human prostate cancer cells in vivo and in vitro. RESULTS: 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 cells in PC-3 xenografts, representative of increased tumor angiogenesis. Mechanistically, PKCδ activation increased the levels of reactive oxygen species (ROS) by binding to and phosphorylating NADPH oxidase, which induced its activity. Also, PKCδ-induced activation of NADPH oxidase increased the level of HIF-1α. CONCLUSIONS: Our results using tumors from the PC-3 xenograft model suggest that PKCδ activation increases angiogenic activity in androgen-independent PC-3 prostate cancer cells by increasing NADPH oxidase activity and HIF-1α levels and thus may partly be responsible for increased angiogenesis in advanced prostate cancer.
BACKGROUND:PKCδ is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells. METHODS: Here, we investigated the role of PKCδ on the growth of PC-3human prostate cancer cells in vivo and in vitro. RESULTS: 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 cells in PC-3 xenografts, representative of increased tumor angiogenesis. Mechanistically, PKCδ activation increased the levels of reactive oxygen species (ROS) by binding to and phosphorylating NADPH oxidase, which induced its activity. Also, PKCδ-induced activation of NADPH oxidase increased the level of HIF-1α. CONCLUSIONS: Our results using tumors from the PC-3 xenograft model suggest that PKCδ activation increases angiogenic activity in androgen-independent PC-3prostate cancer cells by increasing NADPH oxidase activity and HIF-1α levels and thus may partly be responsible for increased angiogenesis in advanced prostate cancer.
Authors: Quinten F M Remijsen; Alexandre Fontayne; Fons Verdonck; Elke Clynen; Liliane Schoofs; Jean Willems Journal: FEBS Lett Date: 2006-10-19 Impact factor: 4.124
Authors: Christopher L Murriel; Eric Churchill; Koichi Inagaki; Luke I Szweda; Daria Mochly-Rosen Journal: J Biol Chem Date: 2004-08-31 Impact factor: 5.157
Authors: So Dug Lim; Carrie Sun; J David Lambeth; Fray Marshall; Mahul Amin; Leland Chung; John A Petros; Rebecca S Arnold Journal: Prostate Date: 2005-02-01 Impact factor: 4.104
Authors: Rachel Bright; Ami P Raval; Jeffrey M Dembner; Miguel A Pérez-Pinzón; Gary K Steinberg; Midori A Yenari; Daria Mochly-Rosen Journal: J Neurosci Date: 2004-08-04 Impact factor: 6.167