Regulation of breast cancer stem cells by E3 ubiquitin ligase CHIP and new anti-cancer drug development
| Project/Area Number |
26670041
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 乳癌 / 癌幹細胞 / ユビキチンリガーゼ / 薬剤耐性 / 創薬 / エストロゲン受容体 / エストロゲン |
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| Outline of Final Research Achievements |
Growing evidence suggest that breast cancer is originated form a minor population which is called cancer stem cells (CSCs). However, there is no agent for CSCs. Here, using microarray screening in aldehyde dehydrogenase (ALDH)-positive CSC model, we identified a novel role for a CHIP/Stub1 ubiquitin ligase in breast CSC regulation. Knockdown of CHIP increased ALDH-positive cells in MCF-7 cells. In contrast, overexpression of CHIP reduced ALDH-positive cells. These data suggest that CHIP negatively regulate breast CSCs. We next examined the effect of compounds that increase expression levels of CHIP. The compound decreased the proportion of ALDH-positive cells in MCF-7 cells. Since knockdown of CHIP did not affect the target gene for the stem cell signaling pathway (Notch, Hedgehog, and Wnt), CHIP is considered to regulate other stem cell target. Taken together, our findings suggest a novel target of CHIP in breast CSCs. CHIP might be a target for drug development against breast cancer.
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Report
(3 results)
Research Products
(24 results)
