Development of radiation sensitization for cancer cells based on cell cycle-dependent DNA repair system
| Project/Area Number |
18K18192
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 63020:Radiation influence-related
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
Sunada Shigeaki 東京医科歯科大学, 難治疾患研究所, 助教 (70807677)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | G2/M細胞周期アレスト / CDK1阻害剤 / 相同組換え修復 / 放射線感受性 / G2/M期細胞周期アレスト / DNA修復 / 細胞周期 / 遺伝性乳がん・卵巣がん |
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| Outline of Final Research Achievements |
We investigated how a CDK1 inhibitor affects DNA damage response in the interaction between cell cycle and DNA repair. The inhibitor blocked DNA repair capacity in dose dependent manner. However, relatively high dose of the inhibitor that induced G2/M cell cycle arrest showed a radio-resistance effect despite low does showed radio-sensitization effect. Then, we found that the high dose of CDK1 inhibitor-induced cell cycle arrest blocked G2/M phase transition with DNA damage and an abberant cell division, resulting in reversible DNA damage sensitivity. In addition, G2 phase cells under the inhibitor treatment likely selected homologous recombination (HR) repair pathway. This selective repair pathway choice caused a high sensitivity to DNA damage in BRCA2 deficient cells because the BRCA2 function was required in HR repair pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、CDK1阻害剤によるG2/M期アレストの誘導は、BRCA2野生型細胞において放射線抵抗性を引き起こし、BRCA2欠損型細胞において放射線感受性を引き起こすことを見出した。細胞周期制御が介入することで、DNA損傷応答が大きく影響されることを示した。また、これらの成果から、HR修復に異常を有する遺伝性乳がん卵巣がんに対して、特異的な放射線増感効果を引き起こす治療戦略の提案が期待される。
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Report
(3 results)
Research Products
(6 results)
