Stabilized beta-catenin promotes hepatocyte proliferation and inhibits TNFalpha-induced apoptosis
- PMID: 14767485
- DOI: 10.1038/labinvest.3700043
Stabilized beta-catenin promotes hepatocyte proliferation and inhibits TNFalpha-induced apoptosis
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.
Similar articles
-
Hepatomegaly in transgenic mice expressing an oncogenic form of beta-catenin.Cancer Res. 2001 Apr 15;61(8):3245-9. Cancer Res. 2001. PMID: 11309273
-
Aberrant expression and function of TCF4 in the proliferation of hepatocellular carcinoma cell line BEL-7402.Cell Res. 2004 Feb;14(1):74-80. doi: 10.1038/sj.cr.7290205. Cell Res. 2004. PMID: 15040893
-
Expression of potential beta-catenin targets, cyclin D1, c-Jun, c-Myc, E-cadherin, and EGFR in chemically induced hepatocellular neoplasms from B6C3F1 mice.Toxicol Appl Pharmacol. 2003 Jul 15;190(2):135-45. doi: 10.1016/s0041-008x(03)00170-4. Toxicol Appl Pharmacol. 2003. PMID: 12878043
-
Beta-catenin and Tcfs in mammary development and cancer.J Mammary Gland Biol Neoplasia. 2003 Apr;8(2):145-58. doi: 10.1023/a:1025944723047. J Mammary Gland Biol Neoplasia. 2003. PMID: 14635791 Review.
-
Control of beta-catenin signaling in tumor development.Ann N Y Acad Sci. 2000 Jun;910:21-33; discussion 33-5. doi: 10.1111/j.1749-6632.2000.tb06698.x. Ann N Y Acad Sci. 2000. PMID: 10911903 Review.
Cited by
-
Transforming growth factor-beta stimulates cyclin D1 expression through activation of beta-catenin signaling in chondrocytes.J Biol Chem. 2006 Jul 28;281(30):21296-21304. doi: 10.1074/jbc.M600514200. Epub 2006 May 10. J Biol Chem. 2006. PMID: 16690606 Free PMC article.
-
HGF/c-Met related activation of β-catenin in hepatoblastoma.J Exp Clin Cancer Res. 2011 Oct 12;30(1):96. doi: 10.1186/1756-9966-30-96. J Exp Clin Cancer Res. 2011. PMID: 21992464 Free PMC article. Clinical Trial.
-
Genetic ablation of β-catenin inhibits the proliferative phenotype of mouse liver adenomas.Br J Cancer. 2014 Jul 8;111(1):132-8. doi: 10.1038/bjc.2014.275. Epub 2014 May 29. Br J Cancer. 2014. PMID: 24874479 Free PMC article.
-
A Boolean model explains phenotypic plasticity changes underlying hepatic cancer stem cells emergence.NPJ Syst Biol Appl. 2024 Sep 2;10(1):99. doi: 10.1038/s41540-024-00422-9. NPJ Syst Biol Appl. 2024. PMID: 39223160 Free PMC article.
-
Repair and regeneration: opportunities for carcinogenesis from tissue stem cells.J Cell Mol Med. 2006 Apr-Jun;10(2):292-308. doi: 10.1111/j.1582-4934.2006.tb00400.x. J Cell Mol Med. 2006. PMID: 16796800 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous
