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- Title
Activation of protein kinase C alpha is required for TPA-triggered ERK (MAPK) signaling and growth inhibition of human hepatoma cell HepG2.
- Authors
Wu Wen-Sheng; Huang Jun-Ming
- 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, PKC α, but not cPKC βII, nPKC ɛ or aPKC ζ 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) PKC α, but not (AS) PKC βII, or nPKC ɛ 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 PKC α is specifically required for TPA-induced ERK(MAPK) signaling to trigger gene expressions of p15INK4band p16INK4a leading to HepG2 growth inhibition.
- Subjects
PROTEIN kinases; HEPATOCELLULAR carcinoma; CELLS; ACETATES
- Publication
Journal of Biomedical Science, 2005, Vol 12, Issue 2, p289
- ISSN
1021-7770
- Publication type
Article
- DOI
10.1007/s11373-005-1210-5