title: PKCδ activation mediates angiogenesis via NADPH oxidase activity in PC-3 prostate cancer cells.
abstract: 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.
authors.affiliation: Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, California 94305-5174, USA.
authors.forename: Jeewon
authors.initials: J
authors.lastname: Kim
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Koyanagi
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019255:NADPH Oxidases / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000201:enzymology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000201:enzymology* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D019255:NADPH Oxidases; D051745:Protein Kinase C-delta