COOH-terminal truncated HBV X protein plays key role in hepatocarcinogenesis

被引:136
作者
Ma, Ning-Fang [1 ,2 ]
Lau, Sze Hang [3 ]
Hu, Liang [3 ]
Xie, Dan [1 ]
Wu, Jun [5 ,6 ]
Yang, Jun [5 ,6 ]
Wang, Yi [7 ]
Wu, Meng-Chao [7 ]
Fung, Jackie [2 ]
Bai, Xueyan [5 ,6 ]
Tzang, Chi-Hung [4 ]
Fu, Li [2 ]
Yang, Mengsu [4 ]
Su, Yan An [5 ,6 ]
Guan, Xin-Yuan [1 ,3 ]
机构
[1] Sun Yat Sen Univ, State Key Lab Oncol So China, Ctr Canc, Guangzhou 510060, Guangdong, Peoples R China
[2] Guangzhou Med Univ, Dept Histol & Embryol, Guangzhou, Guangdong, Peoples R China
[3] Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China
[4] City Univ Hong Kong, Dept Biol & Chem, Hong Kong, Hong Kong, Peoples R China
[5] George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC USA
[6] George Washington Univ, Sch Med, Catherine Birch McCormick Genom Ctr, Washington, DC USA
[7] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Shanghai, Peoples R China
关键词
D O I
10.1158/1078-0432.CCR-07-5082
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: X protein (HBx), a product of hepatitis B virus, has been closely associated with the development of hepatocellular carcinoma (HCC). Based on observations that the COOH-terminal truncated HBx was frequently detected in HCC, the aim of this study is to evaluate the function of COOH-terminal truncated HBx in hepatocarcinogenesis. Experimental Design: Expression pattern of HBx was analyzed by immunohistochemistry on tissue microarray containing 194 pairs of HCCs and their matched nonturnor liver tissues. MIHA and HepG2 cells transfected with full-length (X2) and COOH-terminal truncated HBx (X1) were tested for their ability to grow in soft agar and form tumors in vivo. Proliferation and apoptosis were assessed using 2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide inner salt and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays, respectively. To gain additional insight, the expression profile of HepG2-X2 and HepG2-X1 were compared using cDNA microarray. Results: COOH-terminal truncated HBx was frequently detected in HCCs (79.3%, n = 111), and our in vitro and in vivo studies showed that the truncated rather than the full-length HBx could effectively transform immortalized liver cell line MIHA. Interestingly, expression profiling revealed differential expression of key genes implicated in the control of cell cycle and apoptosis. Conclusions: These findings strongly suggest that the COOH-terminal truncated HBx plays a critical role in the HCC carcinogenesis via the activation of cell proliferation.
引用
收藏
页码:5061 / 5068
页数:8
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