| Project/Area Number |
23590919
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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 |
Gastroenterology
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| Research Institution | Kyushu University |
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Principal Investigator |
TAKAISHI Shigeo 九州大学, 学内共同利用施設等, 准教授 (20596829)
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| Research Collaborator |
WANG Timothy C. コロンビア大学, 医学部消化器内科, 教授
HAYAKAWA Yoku コロンビア大学, 医学部消化器内科, 主任研究員
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 胃発癌マウス / 胃前庭部上皮幹細胞 / Lgr5陽性細胞 / ガストリン/CCK２受容体 / プロガストリン / ヘリコバクター菌感染 / 発癌物質メチルニトロソウレア / CCK２受容体阻害薬YF476 / ガストリン/CCK2受容体 / 国際情報交換（アメリカ合衆国） / 国際情報交換、アメリカ合衆国 / 「国際情報交流、アメリカ合衆国」 / 国際情報交流、アメリカ合衆国 |
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| Outline of Final Research Achievements |
We found that gastrin/CCK2-receptor (CCK2R) defines antral stem cells at position +4, which overlapped with an Lgr5 negative or low cell population but was distinct from typical antral Lgr5 high stem cells. Treatment with progastrin interconverts Lgr5 negative or low, CCK2R positive cells into Lgr5 high cells, increases CCK2R positive cell numbers and promotes gland fission and carcinogenesis in response to the chemical carcinogen MNU. Pharmacological inhibition or genetic ablation of CCK2R attenuated progastrin-dependent stem cell expansionand carcinogenesis.
In summary, CCK2R labels +4 antral stem cells that can be activated and expanded by progastrin, thus identifying one hormonal trigger for gastric stem cell interconversion and a potential target for gastric cancer chemoprevention and therapy.
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