...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Protein kinase C|[epsiv]| interacts with Bax and promotes survival of human prostate cancer cells
【24h】

Protein kinase C|[epsiv]| interacts with Bax and promotes survival of human prostate cancer cells

机译：蛋白激酶C | [epsiv] |与Bax相互作用并促进人类前列腺癌细胞的存活

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Prostatic glandular epithelial cells express protein kinase C (PKC), an oncoprotein that coordinately disrupts the reactivation of the tumor suppressor Rb, derepressess transcriptional elongation of the c-myc oncogene, and propagates survival signals in LNCaP cells. Since the activation of such a program may contribute to the progression of human prostate cancer, a proteomic analysis was performed to gain a more global perspective on the signaling network that PKC might be capable of engaging in prostate cancer cells. Using CWR22 xenografts, we identified at least 18 different structural, signaling, and stress-related proteins that associated with PKC, including an interaction with the proapoptotic protein Bax that was novel to recurrent CWR22 tumors. An investigation into the biological significance of the PKC association with Bax provided the first evidence of an inverse relationship between endogenous levels of PKC and susceptibility of prostate cancer cells to the apoptotic effects of phorbol esters. Western blot and antisense experiments demonstrated that CWR-R1 cells expressed moderate levels of PKC and relied on this protein to survive in the presence of phorbol esters, while the apoptosis normally induced by phorbol esters in PKC-deficient LNCaP cells was dependent on the presence of Bax. Forced expression of PKC in LNCaP cells was sufficient to confer a significant resistance to phorbol esters and this resistance was associated with an inhibition of phorbol ester-induced Bax conformational rearrangements that are important for Bax oligomerization, mitochondrial integration, and cytochrome c release. Considered in their entirety, our data suggest that an association of PKC with Bax may neutralize apoptotic signals propagated through a mitochondrial death-signaling pathway.
机译：前列腺腺上皮细胞表达蛋白激酶C（PKC），这是一种癌蛋白，可协同破坏肿瘤抑制因子Rb的活化，抑制c-myc癌基因的转录伸长，并在LNCaP细胞中传播生存信号。由于此类程序的激活可能有助于人类前列腺癌的发展，因此进行了蛋白质组学分析，以更全面地了解PKC可能参与前列腺癌细胞的信号传递网络。使用CWR22异种移植物，我们鉴定了至少18种与PKC相关的不同结构，信号传导和应激相关蛋白，包括与复发性CWR22肿瘤新颖的促凋亡蛋白Bax的相互作用。对PKC与Bax结合的生物学意义的研究提供了第一个证据，证明内源性PKC水平与前列腺癌细胞对佛波酯的凋亡作用之间存在反比关系。 Western印迹和反义实验表明，CWR-R1细胞表达中等水平的PKC，并依赖该蛋白在存在佛波酯的情况下存活，而佛波酯通常在PKC缺失的LNCaP细胞中诱导的凋亡取决于是否存在PKC。巴克斯LNCaP细胞中PKC的强制表达足以赋予对佛波酯的显着抗性，并且这种抗性与抑制佛波酯诱导的Bax构象重排有关，这对于Bax寡聚化，线粒体整合和细胞色素c释放很重要。从整体上考虑，我们的数据表明PKC与Bax的关联可能会中和通过线粒体死亡信号通路传播的凋亡信号。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号