| Project/Area Number |
16H04693
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MIKI Yoshio 東京医科歯科大学, 難治疾患研究所, 教授 (10281594)
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| Co-Investigator(Kenkyū-buntansha) |
中西 啓 東京医科歯科大学, 難治疾患研究所, 准教授 (50321790)
高岡 美帆 東京医科歯科大学, 難治疾患研究所, 助教 (90770701)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | がん抑制遺伝子 / BRCA1/2 / 合成致死療法 / 乳がん / PARP阻害剤 / BRCA遺伝子 / DNA 損傷修復 / がん / 遺伝子 / BRCA2 / 抗がん剤 / 癌 |
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| Outline of Final Research Achievements |
(1) We identified a microtubule-related protein that directly binds to microtubules together with the microtubule depolymerization inhibitor, paclitaxel, in concert to promote microtubule stabilization. In addition, cell-based and in vitro tubulin polymerization assays revealed that these proteins induced microtubule stabilization.
(2) We identified the nuclear transport protein of BRCA2. Since DNA damage repair is performed in the nucleus, it was found that knockdown of this protein prevents BRCA2 from translocating to the nucleus, BRCA2 cannot function in the nucleus, and synthetic lethality is induced by PARP inhibitors. In addition, we detected two compounds that inhibit the nuclear localization of this protein.
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| Academic Significance and Societal Importance of the Research Achievements |
本申請研究の目的は、BRCAの染色体安定性維持に関わる分子の生理活性を明らかにすることで、目的の分子によって担われる情報伝達の流れが、乳がん発生機構の解明に繋がることが期待される。重要なことは、その結果、得られた情報を駆使して、合成致死理論に基づく新規分子標的の探索や治療法の開発を進める点で、さらに、その中でも特記すべき独創性は、遺伝性乳がん研究から創出された新規治療法を一般乳がんに応用・展開する点であり、基礎医学的興味に留まらず、臨床的な新規診断・治療法開発に強く波及し得るものと確信する。
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