Molecular and Cellular Biochemistry

, Volume 231, Issue 1–2, pp 155–161 | Cite as

Activation of the human transforming growth factor alpha (TGF-α) gene by the hepatitis B viral X protein (HBx) through AP-2 sites

  • Jun Hwan Kim
  • Hyune Mo Rho


The HBx protein is known as a transactivator and potential oncogene, and TGF-α as a potent mitogen in hepatocellular carcinoma. By assays of serial deletion of the promoter of TGF-α gene and the cotransfection of HBx and AP-2 expression vectors, we observed that the HBx significantly activated the promoter activity through AP-2 sites located in the proximal region of the TGF-α promoter (−136 to −30). This effect was also observed in the heterologous promoter assay system containing AP-2 sites. The mutation analyses of three AP-2 sites in the promoter revealed that all three AP-2 sites contributed to the activation of the TGF-α gene in the presence of HBx. Accordingly, the mRNA level of TGF-α was significantly elevated in the HBx-expressing cell, HepG2-HBx and the HBV-producing cell, HepG2-K8. These results suggest that the HBx protein could increase the mitogenic effect of TGF-α by the transactivation of the gene through AP-2 binding sites and consequently, these interactions may accelerate the process of hepatocarcinogenesis.

hepatitis B virus HBx transforming growth factor alpha hepatocellular carcinoma transactivation AP-2 


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© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Jun Hwan Kim
  • Hyune Mo Rho

There are no affiliations available

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