| Project/Area Number |
16H05293
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
池嶋 健一 順天堂大学, 医学部, 教授 (20317382)
山科 俊平 順天堂大学, 医学部, 准教授 (30338412)
今 一義 順天堂大学, 医学部, 准教授 (30398672)
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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 |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥12,610,000 (Direct Cost: ¥9,700,000、Indirect Cost: ¥2,910,000)
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| Keywords | オートファジー / 核マトリクス蛋白 / バイオマーカー / 膵癌 / 肝癌 / 核マトリクス / 膵炎 |
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| Outline of Final Research Achievements |
Three nuclear matrix proteins, 14-3-3ζ, Importin-α4 and Importin-β1, were identified in liver and pancreatic tumor cell lines as autophagy-related proteins. These proteins were confirmed to be expressed in the nucleus of cancer cells in several pancreatic cancer tissues. These nuclear matrix proteins were thought to be involved in cell proliferation and cell death suppression. This feature was strongly confirmed in cell lines in which p62 expression is particularly increased in the cytoplasm, so it was suggested that nuclear accumulation of 14-3-3ζ, Importin-α4 and Importin-β1 cooperates with the p62 protein to enhance cell proliferation and to suppress cell death. Since accumulation of p62 protein in cytoplasm affects cell proliferation through Nrf2-Notch signal activation, cell growth promotion and cell death inhibitory effects induced by nuclear accumulation of 14-3-3ζ, Importin α4 and Importin β1 might be related to Nrf2-Notch signal activation.
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| Academic Significance and Societal Importance of the Research Achievements |
肝腫瘍細胞株と膵腫瘍細胞株においてオートファジー機能障害と関連する共通の核マトリクス蛋白として同定された14-3-3ζ、Importinα４、Importinβ１は、いくつかの膵癌組織において核内発現が確認された。これらの蛋白の核内発現は細胞増殖や細胞死抑制に作用すると考えられることから、これらの核マトリクス蛋白は消化器難病疾患である肝癌・膵癌の診断マーカーとしてだけでなく、治療標的としても有望と考えられ、社会的にも有用な研究結果と考えられた。オーファジー研究において核の不溶分画解析の報告はなく学術的にも重要な研究と考えられる。
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