1. Stabilized beta-catenin promotes hepatocyte proliferation and inhibits TNFalpha-induced apoptosis.
- Author
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Shang XZ, Zhu H, Lin K, Tu Z, Chen J, Nelson DR, and Liu C
- Subjects
- Animals, Apoptosis drug effects, Carcinoma, Hepatocellular etiology, Cell Division, Cell Line, Cell Line, Tumor, Cell Transformation, Neoplastic, Cyclin D1 genetics, Cytoskeletal Proteins chemistry, Cytoskeletal Proteins genetics, Drug Stability, Gene Expression Regulation, Genes, myc, Humans, Liver Neoplasms etiology, Mice, Mice, SCID, Mutation, Trans-Activators chemistry, Trans-Activators genetics, Transfection, Tumor Necrosis Factor-alpha pharmacology, beta Catenin, Cytoskeletal Proteins physiology, Hepatocytes cytology, Hepatocytes physiology, Trans-Activators physiology
- Abstract
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 beta-catenin mutations are identified in up to 30% of HCC and 80% of hepatoblastoma, suggesting a potential role of beta-catenin in the pathogenesis of liver cancers. To define the biological role of the stabilized beta-catenin in liver cell growth and transformation, we examined the effect of mutant beta-catenin on an immortalized murine hepatocyte cell line, AML12. A cell line that stably expresses mutant beta-catenin was established. The cell proliferation, apoptosis, and cell transformation of this cell line were characterized. Our data indicate that the stabilized beta-catenin enhances hepatocyte proliferation, suppresses TNFalpha/Act D-induced cell apoptosis, and causes weak anchorage-independent cell growth. The stabilized beta-catenin-containing cells did not develop tumor in immune-deficient mice. The target genes, c-myc and cyclin D1, were activated by beta-catenin in the hepatocytes. Our study suggests that mutant beta-catenin can promote cell proliferation and cell survival ability, but the stabilized beta-catenin alone is insufficient for completely oncogenic transformation.
- Published
- 2004
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