Integrity of erythrocytes of hypercholesterolemic rats during spices treatment

The HBx protein is known as a transactivator and potential oncogene, and TGF- as a potent mitogen in hepatocellular carcinoma. By assays of serial deletion of the promoter of TGF- 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- 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- gene in the presence of HBx. Accordingly, the mRNA level of TGF- 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- by the transactivation of the gene through AP-2 binding sites and consequently, these interactions may accelerate the process of hepatocarcinogenesis.