Department of Chemical and Systems Biology, Stanford University, School of Medicine, Stanford, California 94305-5174, USA.
Prostate. 2011 Jun 15;71(9):946-54. doi: 10.1002/pros.21310. Epub 2010 Nov 23.
PKCδ is generally known as a pro-apoptotic and anti-proliferative enzyme in human prostate cancer cells.
Here, we investigated the role of PKCδ on the growth of PC-3 human prostate cancer cells in vivo and in vitro.
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.
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.
蛋白激酶 C δ（PKCδ）通常被认为是人类前列腺癌细胞中的促凋亡和抗增殖酶。
在这里，我们研究了 PKCδ 在体内和体外对 PC-3 人前列腺癌细胞生长的作用。
我们发现，持续用特定的 PKCδ 激活剂（活性 C 激酶的ψδ 受体，ψδRACK）处理可增加 PC-3 异种移植物的生长。PC-3 异种移植物中 HIF-1α、血管内皮生长因子和 CD31 阳性细胞的水平增加，代表肿瘤血管生成增加。在机制上，PKCδ 通过与 NADPH 氧化酶结合并使其磷酸化而增加活性氧（ROS）的水平，从而诱导其活性。此外，PKCδ 诱导的 NADPH 氧化酶激活增加了 HIF-1α 的水平。
我们使用来自 PC-3 异种移植模型的肿瘤的结果表明，PKCδ 激活通过增加 NADPH 氧化酶活性和 HIF-1α 水平来增加雄激素非依赖性 PC-3 前列腺癌细胞的血管生成活性，因此可能部分负责晚期前列腺癌中血管生成的增加。
