| Project/Area Number |
25840015
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular biology
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
HIROAKI Fujimori 独立行政法人国立がん研究センター, 研究所, 研究員 (00590043)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | PARP阻害剤 / PARP / Dnmt3 / DNAメチル化 |
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| Outline of Final Research Achievements |
Epigenetic factors are recently noticed as significant targets for anti-cancer therapy, in which the utility of DNMT 3 inhibition has been demonstrated. It is because DNMT3 overexpressing in several tumors inactivated multiple tumor suppressor genes in methylation-dependent manner and DNMT3 dysfunction in these cancer cells induced cancer cell death through recovering expression of tumor suppressor genes. However, specific DNMT3 inhibitor is now under development. In this study, we demonstrated that Parp-1 is required for Dnmt3 expression in vitro and in vivo and that PARP inhibition suppressed A549 proliferation through reduction of the DNMT3B expression. Since PARP inhibitor demonstrated the significant anti-tumor effect to BRCA-/- cancers with few side effect, enlarged application of the inhibitor with other clinical protocols is hoped. Our current study shows the possibility that PARP inhibitor works as an epigenetic anti-cancer drug for DNMT3 overexpressing tumor.
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