Function of histone methyltransferase PR-set7 and its relationship to carcinogenesis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460382
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: National Hospital Organization, Kyushu Cancer Center
• Principal Investigator: Oda Hisanobu 独立行政法人国立病院機構(九州がんセンター臨床研究センター), その他部局等, 連携研究員 (30295133)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ヒストンメチル化酵素 / 癌幹細胞 / 肝臓癌

Outline of Final Research Achievements

PR-SET7-mediated histone 4 lysine 20 methylation has been implicated in maintaining genome integrity. Hepatocyte-specific deletion of PR-SET7 in mouse embryos resulted in G2 phase arrest followed by massive cell death and defect in liver organogenesis. Inactivation at postnatal stages caused cell duplication-dependent hepatocyte necrosis, accompanied by inflammation, fibrosis and compensatory growth induction of neighboring hepatocytes and resident ductal progenitor cells. Prolonged necrotic regenerative cycles coupled with oncogenic STAT3 activation led to the spontaneous development of hepatic tumors composed of cells with cancer stem cell characteristics. These include a capacity to self-renew in culture or in xenografts and the ability to differentiate to phenotypically distinct hepatic cells. Hepatocellular carcinoma in PR-SET7-deficient mice displays a cancer stem cell gene signature specified by the co-expression of ductal progenitor markers and oncofetal genes.

Free Research Field

医化学、分子生物学