PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells
PTEN modulates hepatitis B virus-X protein induced survival signaling in Chang liver cells
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DOI：
10.1016/j.virusres.2006.06.010
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发表时间：
2006-12-01
期刊：
影响因子：
5
通讯作者：
Lee, Young I.
中科院分区：
文献类型：
--
作者：
Kang-Park, Sukmi;Im, Jee H.;Lee, Young I.
PTEN基因是一种新的抑癌基因，在包括肝细胞癌（HCC）在内的多种恶性肿瘤中常发生突变或缺失。我们先前报道了人肝炎B病毒-X（HBx）蛋白通过在肝细胞中不依赖于p53的-PI 3 K-Akt-Bad信号传导实现了对凋亡性细胞死亡的保护（JBC; 276，16969（2000））。在这份报告中，我们证明了在Chang肝细胞（CHL）中PTEN对HBx诱导的抗凋亡信号传导的作用。PTEN在CHL细胞中的表达下调HBx诱导的PI 3 K、Akt活性、Akt、Bad磷酸化，降低caspase 3活性和保护免于DNA片段化。在细胞周期分析中，PTEN对CHL细胞生长在G1期的抑制（JBC; 278，4057（2003））被HBx活化的Akt/PKB克服，这进一步证实了相同的PI 3 K/Akt途径通过HBx和PTEN参与细胞存活和凋亡。PTEN通过PI 3 K途径抑制HBx介导的细胞存活是特异性的，因为PTEN不抑制HBx对Fas介导的细胞凋亡的保护作用。总之，这些发现表明，PTEN有效地调节HBx介导的信号传导，并且是抑制由HBV感染引起的HCC形成的治疗方法中的可行靶点。(c)2006 Elsevier B. V.保留所有权利。
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.