title: A novel mutant 10Ala/Arg together with mutant 144Ser/Arg of hepatitis B virus X protein involved in hepatitis B virus-related hepatocarcinogenesis in HepG2 cell lines.
abstract: Hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC) represents a major health problem worldwide. HBV X (HBx) protein is the most common open reading frame that may undergo mutations, resulting in the development of HCC. This study aimed to determine specific HBx mutations that differentiate the central- and para-tumor tissues, and identify their association with HCC development. HBx gene from HCC tumor and para-tumor tissues of 47 HCC patients was amplified, sequenced and statistically analyzed. A novel combination of 2 mutations at residues 10 and 144 was identified which might play a significant role in HCC development. Expression vectors carrying HBx with the specific mutations were constructed and transfected into HepG2 and p53-null HepG2 cells. Compared to wild type (WT) and single mutation of HBx at residue 10 or 144, the 10/144 double mutations strongly up-regulated p21 expression and prolonged G1/S transition in WT- and p53-null HepG2 cells. Apoptosis was also inhibited by HBx harboring 10/44 double-mutation. Binding of 10/144 double-mutant HBx to p53 was lower than WT HBx. Conclusively, the 10/144 double mutation of HBx might play a crucial role in HCC formation.
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China; Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Changping District Hospital, Beijing 102200, China.
authors.forename: Yuhe
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.
authors.forename: Anna
authors.initials: A
authors.lastname: Wang
authors.affiliation: Shandong Cancer Hospital and Institute, Jinan, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Guo
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China.
authors.forename: Feili
authors.initials: F
authors.lastname: Wei
authors.affiliation: Department of General Surgery, Changping District Hospital, Beijing 102200, China.
authors.forename: Sanjay R
authors.initials: SR
authors.lastname: Mehta
authors.affiliation: San Diego Veterans Affairs Medical Center, La Jolla, CA, USA; Division of Infectious Diseases, University of California, San Diego, CA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Espitia
authors.affiliation: San Diego Veterans Affairs Medical Center, La Jolla, CA, USA; Division of Infectious Diseases, University of California, San Diego, CA, USA.
authors.forename: Davey M
authors.initials: DM
authors.lastname: Smith
authors.affiliation: Department of Infectious Diseases, The Third Hospital of Changzhou, Changzhou Institute of Hepatology, Changzhou City 213001, Jiangsu Province, China. Electronic address: ssewllg@163.com.
authors.forename: Longgen
authors.initials: L
authors.lastname: Liu
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China; Department of Infectious Diseases, The Third Hospital of Changzhou, Changzhou Institute of Hepatology, Changzhou City 213001, Jiangsu Province, China. Electronic address: zhangyulin1968@126.com.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Capital Medical University Affiliated Beijing Youan Hospital, Beijing Institute of Hepatology, Beijing 100054, China. Electronic address: dexi0963@yahoo.com.
authors.forename: Dexi
authors.initials: D
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002453:Cell Cycle; D049109:Cell Proliferation; D002472:Cell Transformation, Viral; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D005838:Genotype; D056945:Hep G2 Cells; D006509:Hepatitis B / Q000150:complications / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics*; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; D051028:bcl-2-Associated X Protein; C057628:hepatitis B virus X protein
keywords: Hepatitis B virus; Hepatocellular carcinoma; Mutation