Development of a liver carcinogenesis model using human hepatocytes and searching suitable anti-cancer drugs considering mutated genes.

Research Project

Project/Area Number	15K15291
Research Category	Grant-in-Aid for Challenging Exploratory Research
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	Osaka University
Principal Investigator	Hayato Hikita 大阪大学, 医学系研究科, 助教 (20623044)
Co-Investigator(Kenkyū-buntansha)	巽智秀大阪大学, 医学系研究科, 講師 (20397699)
Research Collaborator	Kazuhiro Murai 大阪大学, 大学院医学系研究科, 大学院生
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	肝細胞癌
Outline of Final Research Achievements	：Humanized chimeric mice can be prepared by introducing primary human hepatocytes into the TK-NOG mice from the spleen via the portal vein after inducing hepatic injury, and tumors derived from human primary hepatocytes do not occur. However, when human hepatocytes cultured under the special condition were transplanted, tumors were observed in part. The tumors were derived from human hepatocytes because they were positive for HLA. The histology of the tumors was similar to that of human hepatocellular carcinoma. We compared the tumors with human cell before culturing and human hepatocytes just before administration by exome sequence. As a result, the missense mutation (Q61L) was observed in NRas in the tumors. This mutation is the most commonly occurring NRas activating mutation in various cancers. NRas mutation in human hepatocytes administered was considered to be one of the causes of tumorigenesis.