Role of PKC-Isoforms in the Regulation of the Tumor Suppressor PDCD4 in Human Hepatocellular Carcino

• 作 者: SachikoMatsuhashi;
• 机 构: Department of Internal Medicine Saga Medical School Saga University Saga Japan
• 出 处: BIT‘s2nd Annual World Cancer Congess-2009 (2009第二届癌症大会)
• 发表日期: 2009年期

　　Programmed cell death 4 (PDCD4) is classified as a translation regulator and was reported to inhibit the carcinogenesis promoted by the tumor promoter 12-O-tetradecanoilphorbol-13-acetate (TPA), a known protein kinase C (PKC) stimulator.PDCD4 expression was shown to be down-regulated in many tumor tissues including hepatocellular carcinoma (HCC), while mutations or LOH of the gene have not been reported in the tumors.Instead, gene expression was easily regulated by many factors, such as growth factors, interleukins, retinoid, TPA and myb.On the phosphorylation of ser67 by the protein kinase S6K1 activated through the growth factor-activated Akt-mTOR signaling pathway, the PDCD4-protein is triggered to be ubiquitinated by the ubiquitin ligase SCFBTRCP and degraded in a proteasome, stimulating some kinds of protein synthesis and cell proliferation.Recently, we have shown that PDCD4 is involved in the TGF-betal-induced apoptosis of HCC cells and over-expression of the gene induces apoptosis in tumor cells.