| Project/Area Number |
25462604
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | 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 |
YOSHIDA SHOZO 奈良県立医科大学, 医学部, 研究員 (40347555)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Hiroshi 奈良県立医科大学, 医学部, 教授 (40178330)
OI Hidekazu 近畿大学, 医学部附属病院, 教授 (10283368)
YOSHIMOTO Chiharu 奈良県立医科大学, 医学部, 助教 (00526725)
赤坂 珠理晃 奈良県立医科大学, 医学部, 助教 (90526724)
重富 洋志 奈良県立医科大学, 医学部, 助教 (20433336)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 卵巣明細胞腺癌 / HNF-1beta / チェックポイント機構 / Chk1 / Claspin / Usp28 / 発癌機序 |
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| Outline of Final Research Achievements |
Ovarian clear cell adenocarcinoma (OCCA) shows anticancer drug resistance. We reported that HNF-1beta might sustain Chk1 protein phosphorylation to arrest the cell cycle and inhibit cell death induced by an anticancer agent. As the mechanism of sustained Chk1 phosphorylation, we showed that HNF-1beta inhibited the ubiquitylation of Claspin through the overexpresses Usp28 which was a deubiquitinating enzyme. Transient knocking-down of Claspin or Usp28 in HNF-1beta expressing cells increased cell death and improved chemoresistance after the addition of bleomycin which oxidatively cleaved DNA. Combination anticancer drugs with Chk1 inhibitors also induced cell death and increased chemosensitivity. Usp28, Claspin and Chk1 may be new targets of treatment in OCCA.
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