| Project/Area Number |
26293361
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉元 千陽 奈良県立医科大学, 医学部, 助教 (00526725)
重富 洋志 奈良県立医科大学, 医学部, 助教 (20433336)
吉田 昭三 奈良県立医科大学, 医学部, 研究員 (40347555)
小池 奈月 奈良県立医科大学, 医学部, 助教 (20526785)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2014: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
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| Keywords | 子宮内膜症 / 卵巣癌 / 癌 / 子宮内膜症癌化 |
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| Outline of Final Research Achievements |
Hepatocyte nuclear factor (HNF)-1beta enhances checkpoint kinase 1 (Chk1) activation and promotes G2/M cell cycle progression in ovarian clear cell carcinoma (CCC) following exposure to diverse genotoxic agents including bleomycin. Loss-of-function studies using RNAi-mediated gene silencing indicated that HNF-1beta facilitated the Claspin expression after treatment with a genotoxic agent bleomycin, resulting in accumulation of phosphorylated Chk1 (p-Chk1) and promotion of survival in CCC cell lines. This study showed for the first time that USP28, a de-ubiquitinase crucial for Claspin expression, is one target gene of HNF-1beta. Knockdown of endogenous USP28 suppressed the Claspin and p-Chk1 expression and cell viability. Our findings identify a novel pathway of the HNF-1beta―Claspin―Chk1 axis in checkpoint signal amplification in response to DNA damage. Targeting this pathway may represent a putative, novel, anticancer strategy in CCC.
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