Cell and tissue type dependency of activated Ras in carcinogenesis
Project/Area Number |
17H04991
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Research Category |
Grant-in-Aid for Young Scientists (A)
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Allocation Type | Single-year Grants |
Research Field |
Tumor biology
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Research Institution | National Cancer Center Japan |
Principal Investigator |
Yamamoto Yusuke 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (60768117)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2019: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2018: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2017: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
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Keywords | Ras / 上皮細胞 / 発がん / 組織特異性 / Ras遺伝子 / Ras遺伝子 / 癌 / 遺伝子 |
Outline of Final Research Achievements |
In this research project, we focused on the activated RAS mutations (KRAS, HRAS, NRAS), which have been detected at different mutation rates depending on cancer tissues, and analyzed the oncogenic process using a primary epithelial cell culture system. Analysis with lung epithelial cells confirmed the different oncogenic functions of RAS mutations between bronchial epithelial cells and small airway epithelial cells of the lung. We also searched for small molecules that are selectively effective against specific RAS mutations and identified several candidate compounds. These compounds were found to be effective against RAS mutations in the experiment with cell lines and in a mouse transplantation model.
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Academic Significance and Societal Importance of the Research Achievements |
Ras遺伝子の研究は広く行われているが、組織ごとの発がんへの寄与の違いは未だ解明されていない生物学的な問題である。本研究では、複数種類の上皮細胞を用いて、Ras遺伝子の感受性を総合的に検討し、その機能的な違いを見出した。さらに活性化型Rasを標的とした分子標的型の抗がん剤は長い間、期待されているが未だに開発には至っていない。細胞種ごとの活性化型Rasの指向性を解明することで、選択的に働く下流経路や活性化型Rasを有する細胞の生存に必須な経路を明らかにし、しいてはRas関連分子に対する抗がん剤の開発につながると期待できる。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Cancer Extracellular Vesicles Contribute to Stromal Heterogeneity by Inducing Chemokines in Cancer-Associated Fibroblasts2019
Author(s)
Naito Y, Yamamoto Y, Sakamoto N, Shimomura I, Kogure A, Kumazaki M, Yokoi A, Yashiro M, Kiyono T, Yanagihara K, Takahashi RU, Hirakawa K, Yasui W, Ochiya T.
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Journal Title
Oncogene
Volume: 38
Issue: 28
Pages: 5566-5579
DOI
Related Report
Peer Reviewed / Open Access
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