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Increased expression of ErbB-2 in liver is associated with hepatitis B × antigen and shorter survival in patients with liver cancer
International Journal of Cancer, 07/21/09

Liu J et al. - In a study to determine whether hepatitis B x antigen (HBxAg) was associated with upregulated expression of ErbB-2, these results suggest that ErbB-2/β-catenin up-regulation contributes importantly to the mechanism of HBxAg-mediated hepatocellular growth.

Methods

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.
HBxAg positive and negative HepG2 cells were subjected to proteomics analysis.

Results

ErbB-2 was shown to be upregulated in HepG2X but not control cells.
ErbB-2 was 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 expression of β-catenin, suggesting that ErbB-2 contributed to the stabilization of β-catenin.
ErbB-2-specific siRNA partially blocked the ability of HBxAg to promote DNA synthesis and growth of HepG2 cells.

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