| Project/Area Number |
17K16876
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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 |
Obstetrics and gynecology
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| Research Institution | Miyagi Prefectural Hospital Organization Miyagi Cancer Center |
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Principal Investigator |
Nomura Miyuki 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん薬物療法研究部, 研究技師 (40390893)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | プロテインホスファターゼ / BRCA1 / プロテインホスファターゼ6型 / BRCA / 卵巣がん / PP6 / 婦人科腫瘍学 |
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| Outline of Final Research Achievements |
The tumor suppressor BRCA1 is implicated in homologous recombination, however how BRCA1 is regulated by phosphorylation is not clarified. To get a clue which phosphatase is involved in ovarian carcinogenesis, we screened Prognoscan. The cohort experiment of ovarian cancer (Australia, DATASETGSE9891) suggested that patients with lower Ppp6c expression showed worse prognosis, suggesting that Ppp6c might possess suppressor activity to ovarian cancer. We then co-transfected performed BRCA1 with Ppp6c into cells, and found that BRCA1 is present in Ppp6c immunocomplex, and Ppp6c is present in BRCA1 immunocomplex.
To testify whether Ppp6c function as tumor suppressor, we first used mouse skin carcinogenesis system. Doubly-mutant (K-rasG12D-expressing and Ppp6c-deficient) mice showed early onset tumor formation in the skin than K-rasG12D-expressing mice, suggesting that Ppp6c function as tumor suppressor in the mouse skin.
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| Academic Significance and Societal Importance of the Research Achievements |
BRCA1の異状またはBRCA1が含まれるDNA修復マシナリーの異状が卵巣がんの発生・悪性化の原因となっていることが示唆されている。この病態においては、ポリADPリボース合成酵素阻害剤(PARPI)の投与が奏功する。一方で、PARPIとは異なる機序での治療法の開発が求められている。PP6によるBRCA1のリン酸化による調節は、新たな治療標的となることが期待される。
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