Abstract
Hepatitis B × antigen, or HBxAg, contributes importantly to the pathogenesis of hepatocellular carcinoma (HCC). Given that HBxAg constitutively activates β‐catenin and that upregulated ErbB‐2 promotes β‐catenin signaling in other tumor types, experiments were designed to ask whether HBxAg was associated with upregulated expression of ErbB‐2. When HBxAg positive and negative HepG2 cells were subjected to proteomics analysis, ErbB‐2 was shown to be upregulated in HepG2X but not control cells. ErbB‐2 was also strongly upregulated in HB infected liver, and weakly in some HCC nodules, where it correlated with HBxAg expression. Among tumor bearing patients, strong ErbB‐2 staining in the liver was associated with dysplasia, and a shorter survival after tumor diagnosis. This implies that elevated ErbB‐2 is an early marker of HCC. Treatment of HepG2X cells with ErbB‐2 specific siRNA not only reduced ErbB‐2 expression, but also reduced the expression of β‐catenin, suggesting that ErbB‐2 contributed to the stabilization of β‐catenin. ErbB‐2 specific siRNA also partially blocked the ability of HBxAg to promote DNA synthesis and growth of HepG2 cells. These results suggest that ErbB‐2/β‐catenin up‐regulation contributes importantly to the mechanism of HBxAg mediated hepatocellular growth. © 2009 UICC