This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ma, N.-F. Articles by Guan, X.-Y. PubMed PubMed Citation Articles by Ma, N.-F. Articles by Guan, X.-Y.

COOH-Terminal Truncated HBV X Protein Plays Key Role in Hepatocarcinogenesis

Authors' Affiliations: ¹ State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University; ² Department of Histology and Embryology, Guangzhou Medical College, Guangzhou, China; ³ Department of Clinical Oncology, The University of Hong Kong, and ⁴ Department of Biology and Chemistry, The City University of Hong Kong, Hong Kong; ⁵ Department of Biochemistry and Molecular Biology and the Catherine Birch McCormick Genomics Center, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia; and ⁶ Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China

Requests for reprints: Xin-Yuan Guan, Room 605, State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, 651 East Dongfeng Road, Guangzhou 510060, China. Phone: 852-2819-9785; Fax: 852-2819-9629; E-mail: xyguan{at}hkucc.hku.hk.

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 nontumor 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.