| Project/Area Number |
15K16126
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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 |
Risk sciences of radiation and chemicals
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | DNA損傷トレランス / 薬剤耐性 / 損傷乗り越えDNA合成 / DNAポリメラーゼ / 細胞死 / 突然変異 / DNA修復 / DNA複製 |
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| Outline of Final Research Achievements |
To provide the evidence that DNA damage tolerance (DDT) pathways could be novel targets for cancer therapy, I analyzed the physiological function of REV7 involved in DDT pathways. REV7 was highly expressed in testicular germ cell tumor (TGCT) cells, and depletion of REV7 decreased cell proliferation and enhanced sensitivity to cisplatin. After cisplatin treatment, phosphorylation of H2AX and cleaved-PARP were more increased in REV7 knockdown cells. Additionally, CRISPR/Cas9 inactivation of REV7 in TGCT cells enhanced cisplatin sensitivity of cisplatin-resistant cells as well as cisplatin-sensitive cells. These results indicate that depletion of REV7 enhances sensitivity to cisplatin in TGCTs, suggesting that REV7 is a potential candidate of molecular target for TGCT therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
REV7の機能抑制はシスプラチンの抗腫瘍活性を高めるだけでなく、シスプラチン抵抗性腫瘍に対しても有効であり、DNA損傷トレランスが分子標的として有用であることが示唆された。シスプラチンの腫瘍縮小効果の増強は投薬量の減少につながり、相対的にシスプラチンによる副作用の低減に大きく寄与すると期待される。
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