Activation of protein kinase C alpha is required for TPA-triggered ERK (MAPK) signaling and growth inhibition of human hepatoma cell HepG2

作者：Wu WS; Huang JM

来源：Journal of Biomedical Science, 2005, 12(2): 289-296.

DOI：10.1007/s11373-005-1210-5

• extracellular related kinase
• HepG2 cell
• protein kinase C
• tetradecanoyl phorbol acetate

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 p15(INK4b)and p16(INK4a) CDK inhibitors and growth inhibition of hepatoma cell HepG2 triggered by the tumor promoter tetradecanoyl 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, PKC alpha, but not cPKC beta II, nPKC epsilon or aPKC zeta 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 mu M Bisindolylmaleimides, an inhibitor of PKC, attenuated the TPA-induced phosphorylation of ERK, gene expressions of p15(INK4b) and p16(INK4a) and growth inhibition of HepG2 cell in a dose-dependent manner. Consistently, transfection of HepG2 with 1.0-3.0 mu M antisense (AS) PKC alpha, but not (AS) PKC beta lI, or nPKC epsilon 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 PKCa is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15(INK4b) and p16(INK4a) leading to HepG2 growth inhibition.

• 出版日期2005