| Project/Area Number |
21790649
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Chiba University |
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Principal Investigator |
CHIBA Tetsuhiro Chiba University, 医学部附属病院, 助教 (00381583)
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| Co-Investigator(Renkei-kenkyūsha) |
IWAMA Atsushi 千葉大学, 大学院・医学研究院, 教授 (70244126)
MIYAGI Satoru 千葉大学, 大学院・医学研究院, 助教 (20400997)
YOKOSUKA Osamu 千葉大学, 大学院・医学研究院, 教授 (90182691)
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| Project Period (FY) |
2009 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 癌幹細胞 / 肝臓癌 / ポリコーム群遺伝子 / 自己複製能 / BMI1 / EZH2 / DZNep |
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| Research Abstract |
PcG proteins form chromatin-associated multiprotein complexes, polycomb repressive complex 1 (PRC1) and PRC2 and repress the expression of targets such as Ink4a/Arf genes. Bmi1, a component of PRC1, has been implicated in the regulation of self-renewal in a range of different stem cells including hepatic stem cells. Analyses of Bmi1-deficient and/or Ink4a/Arf-deficient hepatic stem cells revealed that Bmi1 regulates self-renewal and tumorigenicity in both Ink4a/Arf-dependent and -independent manners. Microarray analyses successfully identified 5 down-regulated genes as candidate downstream targets for Bmi1 such as sex determining region Y-box 17 (Sox17).
Loss-of-function assays of Ezh2, a major component of PRC2, also revealed that Ezh2 tightly regulates self-renewal in both normal and cancer stem cells in liver. Moreover, we showed that pharmacological inhibition of EZH2 by an S-adenosylhomocysteine hydrolase inhibitor, 3-deazaneplanocin A (DZNep) is a promising approach for the eradication of liver cancer stem cells.
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