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

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Journal of Biomedical Science

Abstract

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 p15INK4band p16INK4a 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, PKCα, but not cPKCβII, nPKCɛ 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 Bisindolylmaleimides, an inhibitor of PKC, attenuated the TPA-induced phosphorylation of ERK, gene expressions of p15INK4band p16INK4a, 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 nPKCɛ 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.

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  1. Department of Medical Technology, TZU CHI University, Taiwan

    Wu Wen-Sheng & Huang Jun-Ming

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Wen-Sheng, W., Jun-Ming, H. Activation of protein kinase C alpha is required for TPA-triggered ERK (MAPK) signaling and growth inhibition of human hepatoma cell HepG2. J Biomed Sci 12, 289–296 (2005). https://doi.org/10.1007/s11373-005-1210-5

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