Modulation of breast radiation responses by steroid hormones through its action on cancer stem cells
| Project/Area Number |
24710066
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
Vares Guillaume 国立研究開発法人放射線医学総合研究所, 放射線防護研究 センター, 研究員 (10415432)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | cancer stem cell / breast cancer / radiation / progesterone / steroid hormone / microRNA / Cancer stem cells / Breast cancer / Progesterone / Radiation / miRNA / がん幹細胞 / 乳癌 / プロゲステロン / 放射線 / 放射 |
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| Outline of Final Research Achievements |
Progesterone (Pg) stimulated cancer stem cell expansion both in progesterone receptor (PR)-positive breast cancer cells and in PR-negative normal cells. In MCF10A basal-like PR-negative cells, Pg treatment and irradiation triggered cancer and stemness-associated microRNA regulations (such as the downregulation of miR-22 and miR-29c), which resulted in increased proportions of radiation-resistant CSCs. Pg activated the PI3k/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the PI3k/Akt pathway counteracted the generation of CSCs by Pg and irradiation. The stimulation of PI3K/Akt via mPR resulted in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs.
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Report
(5 results)
Research Products
(8 results)
