PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells

被引：22

作者：

Kang-Park, Sukmi

Im, Jee H.

Lee, Je H.

Lee, Young I. ^{[1
]}

机构：

[1] Korea Res Inst Biosci & Biotechnol, Liver Cell Signal Transduct Lab, Mol Canc Res Ctr, Taejon 305606, South Korea

[2] Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea

来源：

VIRUS RESEARCH | 2006年 / 122卷 / 1-2期

关键词：

hepatitis B; virus-X; protein; anti-apoptosis; PTEN; hepatocellular carcinoma;

D O I：

10.1016/j.virusres.2006.06.010

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

PTEN gene, a novel tumor suppressor is frequently mutated or deleted in several malignancies including human hepatocellular carcinoma (HCC). We report previously that human hepatitis B virus-X (HBx) protein achieves protection from apoptotic cell death through-PI3K-Akt-Bad signaling that is p53-independent in liver cells (JBC; 276, 16969 (2000)). In this report, we demonstrated the PTEN effect on HBx induced anti-apoptotic signaling in Chang liver cells (CHL). Expression of PTEN in CHL cells downregulate HBx induced PI3K, Akt activities, Akt, Bad phosphorylations, decreased caspase 3 activity and protection from DNA fragmentations. PTEN suppression of CHL cell growth at G1 phase (JBC;278,4057(2003)) in cell cycle analysis, which is overcome by HBx activated Akt/PKB further confirmed that same PI3K/Akt pathway is involved in cell survival and apoptosis by HBx and PTEN. PTEN suppression of HBx-mediated cell survival through PI3K pathway is specific, since PTEN does not suppress the effect of HBx on the protection from Fas-mediated apoptosis. Taken together, these findings demonstrate that PTEN potently modulate HBx-mediated signaling and is a viable target in therapeutic approaches to inhibit the formation of HCC caused by HBV infections. (c) 2006 Elsevier B.V. All rights reserved.

引用

页码：53 / 60

页数：8

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