The role of Apg-2 in liver steatosis and carcinogenesis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Itoh Yoshito 京都府立医科大学, 医学(系)研究科(研究院), 教授 (70244613)
• Co-Investigator(Kenkyū-buntansha): 山口 寛二 京都府立医科大学, 医学(系)研究科(研究院), 助教 (50381950)
• Co-Investigator(Renkei-kenkyūsha): Fujita Jun 京都大学, 医学研究科, 教授 (50173430) ; Itoh Katsuhiko 京都大学, 医学研究科, 准教授 (90281097)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Apg-2 / 分子シャペロン / 肝癌 / 細胞周期 / ユビキチン化

Outline of Final Research Achievements

Heat shock proteins (HSPs) not only protect cells from the toxic effects of heat and other stresses but also have multiple housekeeping functions, such as folding and protein degradation. Apg-2 is a subfamily of Hsp110 and has been reported to be overexpressed in human hepatocellular carcinomas (HCCs). To study the role of Apg-2 in liver steatosis and carcinogenesis, we generated Apg-2 deficient mice and examined high fat diet-induced liver steatosis and diethylnitrosamine (DEN)-induced hepatocellular carcinomas (HCCs). We found that Apg-2 deficient mice exhibited less liver steatosis and DEN-induced hepatocellular carcinomas (HCCs) compared to wild-types. RNA sequence from Apg-2 deficient HCCs and in vitro study of hepatoma cell lines revealed that Apg-2 regulated cell cycle G2/M pathway-related molecules, such as CDK1/CyclinB1, and promoted HCCs proliferations. These findings indicated that Apg-2 is a potential target for the therapy of HCCs.

Free Research Field

肝臓病学