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HBx-induced reactive oxygen species activates hepatocellular carcinogenesis via dysregulation of PTEN/Akt pathway

查看全文 作　　者：Hye-Lin [1,2]Ha;Dae-Yeul [1,2]Yu 高影响力作者 机构地区：[1]Disease Model Research Laboratory,Aging Research Center,Korea Research Institute of Bioscience and Biotechnology;[2]Department of Functional Genomics,University of Science and Technology高影响力机构 出　　处：《World Journal of Gastroenterology》索引2010年第16卷第39期,共6页高影响力期刊 基　　金：Supported by The 21st century Frontier Program in the Functional Human Genome Project,No.HGM0200934;the International Collaboration Program of Science and Technology,No. FGM0600914;the Research Program for New Drug Target Discovery Grant from the Ministry of Education,Science & Technology,No.NBM3300711;the KRIBB Research Initiative Program Grant,No.KGM3320911 摘　　要：AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis. 关 键 词：Hepatitis B virus X protein HEPATOCELLULAR carcinoma Akt Reactive oxygen species PHOSPHATASE and TENSIN HOMOLOG
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