Role of β-catenin in the liver and liver cancer

Research Project

Project/Area Number	20790315
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Experimental pathology
Research Institution	National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
Principal Investigator	SEKINE Shigeki National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East, 研究所病理部, 室長 (10321879)
Project Period (FY)	2008 – 2009
Project Status	Completed (Fiscal Year 2009)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2008: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords	β-catenin / 肝 / 肝がん
Research Abstract	To systematically identify β-catenin-regulated genes in the liver, a microarray analysis was performed on hepatocyte-specific β-catenin knockout mice. The expression of the identified β-catenin downstream genes were further examined in human hepatocellular carcinoma samples. The result showed that overexpression of a subset of the β-catenin-regulated genes identified in the mouse models correlated closely with the presence of β-catenin gene mutations in human hepatocellular carcinomas. Hepatocyte-specific Dicer knockout mice was found to exhibit impaired localization of periportal genes within the liver lobule. This phenotype partially simulates that of β-catenin knockout mice. Analysis of these two mouse models revealed an essential role of Dicer in the regulation of periportal area-specific gene expression by β-catenin.