| Project/Area Number |
16K09279
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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 | The University of Tokyo |
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Principal Investigator |
Narita Akiko 東京大学, 医学部附属病院, 特任臨床医 (30772917)
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| Co-Investigator(Kenkyū-buntansha) |
平田 喜裕 東京大学, 医科学研究所, 准教授 (10529192)
木下 裕人 公益財団法人朝日生命成人病研究所, その他部局等, 教授(移行) (50645322)
早河 翼 東京大学, 医学部附属病院, 助教 (60777655)
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| Research Collaborator |
KONISHI mitsuru
HATA masahiro
TSUBOI mayo
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | びまん性胃癌 / 印環細胞癌 / 遺伝子 / 分化 / 胃癌 / 遺伝子変異 |
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| Outline of Final Research Achievements |
To identify the role of RhoA Y42C mutation in diffuse type gastric cancer development, mouse with inducible RhoA Y42C expression was established and examined. Gastric pit cell specific RhoA Y42C expression did not generate signet ring cell carcinoma by 24 weeks. Immunohistological evaluation revealed almost identical gastric gland structures to wild type mice. Organoids derived from transgenic mice proliferated with similar proliferation speed and similar stem cell marker expression to wild type organoids.
CDH1 deletion, a causative gene of familial diffuse gastric cancer, in gastric pit cell lineage, transiently generated signet ring cell carcinoma, which was eventually replaced by squamous cell. Additional RhoA Y42C mutation did not enhance signet ring cell carcinoma formation. These results demonstrated that RhoA Y42C mutation is not the driver mutation of diffuse type gastric carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
予後不良癌の代表であるびまん性胃癌の発生機序は十分に解明されていない。近年のゲノムワイドな遺伝子変異解析により、E-cadherinに加えRhoA変異が特徴的にみられることが分かったがその発癌に果たす役割は十分に解明されていなかった。本研究は世界で初めてRhoA変異をマウス胃粘膜に導入しその意義を動物モデルで検討したものである。RhoA変異単独で発癌しなかったという結果は、びまん性胃癌の進展度別遺伝子変異プロファイルにおいてRhoA変異が早期には少ないとする最近の研究結果に合致する有用な結果といえる。
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