- 作者: Wu Wen-Sheng & Huang Jun-Ming
- 作者服務機構: Department of Medical Technology, TZU CHI University, Taiwan
- 中文摘要: --
- 英文摘要: The signaling mechanisms for most of the antiproliferative processes are not fully understood. We have demonstrated that ERK(MAPK) signaling was involved in the induction of both p15INK4b and p16INK4a CDK inhibitors and growth inhibition of hepatoma cell HepG2 triggered by the tumor promoter tetra-decanoyl phorbol acetate (TPA). In this study, the upstream signal mechanism for TPA-induced ERK(MAPK) activation was investigated. In HepG2 cells only one of the cPKC isozymes, PKCα, but not cPKCβII, nPKCε or aPKCζ was activated by TPA as demonstrated by its membrane translocation within 10-30 min and down-regulation at 24 h after TPA treatment. Pretreatment of 0.2-2.0 μM Bisindolylma-leimides, an inhibitor of PKC, attenuated the TPA-induced phosphorylation of ERK, gene expressions of pl5INK4band pl6INK4a; and growth inhibition of HepG2 cell in a dose-dependent manner. Consistently, transfection of HepG2 with 1.0-3.0 μM antisense (AS) PKCα, but not (AS) PKCβII, or nPKCε oligonucleotides (ODN), for 36 h prior to TPA treatment also prevented the TPA-induced molecular and cellular effects described above. Taken together, we concluded that PKCα is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15INK4band p16INK4a leading to HepG2 growth inhibition.
- 中文關鍵字: --
- 英文關鍵字: extracellular related kinase, HepG2 cell, protein kinase C, tetradecanoyl phorbol acetate