| Project/Area Number |
17K07347
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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 |
Functional biochemistry
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Tanabe Kenji 東京女子医科大学, 医学部, 准教授 (80423341)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 上皮成長因子 / 細胞内シグナル伝達 / 画像解析 / ハイコンテントスクリーニング / EGF受容体 / 化合物ライブラリー / シグナル伝達 / 化合物スクリーニング / イメージング解析 / 情報工学 / 細胞・組織 / 数理解析 |
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| Outline of Final Research Achievements |
Epidermal growth factor receptor (EGFR) is one of major driver gene in cancer, and many clinically effective drugs that target EGFR-associated molecules have been developed. In this study, I combined image analysis with unsupervised machine learning to identify novel regulators involved in the EGFR pathway. Lung cancer cell line, A549, was treated with a pharmacologically active compound library to evaluate their target’s role in the pathway. Cells stimulated by EGF were fixed and stained to visualize several signaling proteins. Cell images were analyzed to evaluate cellular phenotype under the treatment of each compound. As result, three structurally different proteasome inhibitors were statistically identified to have an unique cellular phenotype. Proteasomes are known as degradative enzyme complex for ubiquitinated proteins, but its role in the EGFR pathway were still unknown. This study suggests that proteasome is an essential regulator for EGFR pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
EGFRはがんの主要な原因遺伝子の一つであり、その阻害剤が有効な抗がん剤であることが知られている。一方、EGFRの下流に位置するシグナル伝達分子の異常もがんで見つかっており、詳細な分子機構の理解が求められている。本研究では新たな制御因子としてプロテアソームを同定した。本研究で用いた画像解析のアプローチは他の様々な疾患モデルに容易に適用できるため、更なる発展・成果が期待される。
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