Stabilized β-catenin promotes hepatocyte proliferation and inhibits TNFα-induced apoptosis

The human hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The mechanisms of liver cell oncogenic transformation are still unknown. The β-catenin mutations are identified in up to 30% of HCC and 80% of hepatoblastoma, suggesting a potential role of β-catenin in the pathogenesis of liver cancers. To define the biological role of the stabilized β-catenin in liver cell growth and transformation, we examined the effect of mutant β-catenin on an immortalized murine hepatocyte cell line, AML12. A cell line that stably expresses mutant β-catenin was established. The cell proliferation, apoptosis, and cell transformation of this cell line were characterized. Our data indicate that the stabilized β-catenin enhances hepatocyte proliferation, suppresses TNFα/Act D-induced cell apoptosis, and causes weak anchorage-independent cell growth. The stabilized β-catenin-containing cells did not develop tumor in immune-deficient mice. The target genes, c-myc and cyclin D1, were activated by β-catenin in the hepatocytes. Our study suggests that mutant β-catenin can promote cell proliferation and cell survival ability, but the stabilized β-catenin alone is insufficient for completely oncogenic transformation.