Arima Tetsuhiko, Nakao Kazuhiko, Nakata Keisuke, Ishikawa Hiroki, Ichikawa Tatsuki, Hamasaki Keisuke, Ishii Nobuko, Eguchi Katsumi
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.
Int J Mol Med. 2002 Apr;9(4):397-400.
The X-gene product of hepatitis B virus (HBX) modulates a variety of viral and cellular genes relevant to hepatocarcinogenesis, where alpha-fetoprotein (AFP) is produced by hepatoma cells. In the present study, the possible mechanism by which HBX regulates AFP expression was investigated using three human hepatoma cells, HepG2, HuH-7 and Hep3B, which are known to contain the wild-type, the mutant-type and the deletion of p53, respectively. Transfection with the HBX expression vector stimulated the co-transfected AFP reporter gene expression in HepG2 cells and HuH-7 cells, but not in Hep3B cells. Transfection with the p53 expression vector repressed the AFP reporter gene expression in all three hepatoma cells, while overexpression of HBX counteracted the p53-induced repression. In addition, a G-->A substitution at nucleotide -119 in the AFP promoter sequence abrogated the stimulatory effect of HBX on the AFP promoter in HepG2 cells. These results suggest that HBX interacts with p53 to up-regulate AFP gene transcription probably by restoration of the p53-mediated repression of the AFP promotor activity.
乙型肝炎病毒（HBX）的X基因产物可调节多种与肝癌发生相关的病毒和细胞基因，其中甲胎蛋白（AFP）由肝癌细胞产生。在本研究中，利用三种人肝癌细胞HepG2、HuH-7和Hep3B，分别研究了HBX调节AFP表达的可能机制，已知这三种细胞分别含有野生型、突变型和缺失型p53。用HBX表达载体转染可刺激HepG2细胞和HuH-7细胞中共转染的AFP报告基因表达，但对Hep3B细胞无此作用。用p53表达载体转染可抑制所有三种肝癌细胞中的AFP报告基因表达，而HBX的过表达可抵消p53诱导的抑制作用。此外，AFP启动子序列中核苷酸-119处的G→A替换消除了HBX对HepG2细胞中AFP启动子的刺激作用效应。这些结果表明，HBX可能通过恢复p53介导的对AFP启动子活性的抑制作用，与p53相互作用以上调AFP基因转录。
