| Project/Area Number |
25670705
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Nara Medical University |
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Principal Investigator |
AKASAKA Juria 奈良県立医科大学, 医学部, 助教 (90526724)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Chiharu 奈良県立医科大学, 医学部, 助教 (00526725)
OI Hidekazu 近畿大学, 医学部附属病院, 教授 (10283368)
YOSHIDA Shozo 奈良県立医科大学, 医学部, 講師 (40347555)
FURUKAWA Naoto 奈良県立医科大学, 医学部, 講師 (50347556)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 卵巣明細胞腺癌 / HNF-1β / Chk1 / Claspin / チェックポイント / 婦人科腫瘍 / HNF-１beta / チェックポイント機構 / 上皮性卵巣癌 / 明細胞腺癌 / HNF-1beta / ATR / 細胞周期調節 |
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| Outline of Final Research Achievements |
We have found that transcription factor HNF-1β expressed in clear cell adenocarcinoma induced hyperphosphorylation of Chk1 acting on DNA damage checkpoint, leading to acquisition of anticancer drug resistance. Chk1 is activated through the signals from ATM/ATR which recognize damaged DNA sites. Despite knockdown of these proteins, hyperphosphorylation of Chk1 was maintained. With focusing on Claspin, which can form a complex with Chk1 and facilitate its activation, it was found that HNF-1β activated autophosphorylation of Chk1 through the induction of Claspin expression. Accordingly, knockdown of Claspin led to improvement in sensitivity to anticancer drugs. The Clapsin-Chk1 complex was shown to be a novel therapeutic target in the clear cell adenocarcinoma.
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