Function of histone methyltransferase PR-set7 and its relationship to carcinogenesis
| Project/Area Number |
26460382
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | National Hospital Organization, Kyushu Cancer Center |
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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)
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| Co-Investigator(Kenkyū-buntansha) |
中別府 雄作 九州大学, 生体防御医学研究所, 教授 (30180350)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ヒストンメチル化酵素 / 癌幹細胞 / 肝臓癌 / 遺伝子改変マウス / ヒストンメチル化 / 発癌 / エピジェネティクス / PR-Set7 / 肝幹細胞 / 肝発生 / 細胞死 |
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| 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.
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Report
(4 results)
Research Products
(4 results)
