Transactivation of human alpha-fetoprotein gene by X-gene product of hepatitis B virus in human hepatoma cells.
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.
Arima
Tetsuhiko
T
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.
Nakao
Kazuhiko
K
Nakata
Keisuke
K
Ishikawa
Hiroki
H
Ichikawa
Tatsuki
T
Hamasaki
Keisuke
K
Ishii
Nobuko
N
Eguchi
Katsumi
K
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins; D000509:alpha-Fetoproteins / Q000235:genetics* / Q000378:metabolism
D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; D000509:alpha-Fetoproteins; C057628:hepatitis B virus X protein