Analysis of TGF be-ta/EMT axis on the formation of clinically-relevant radioresistant phenotype
| Project/Area Number |
25461871
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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 |
Radiation science
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
FUKUMOTO Manabu 東北大学, 加齢医学研究所, 教授 (60156809)
KUWAHARA Yoshikazu 東北大学, 加齢医学研究所, 助教 (00392225)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 臨床的放射線耐性 / 放射線獲得耐性 / 放射線治療 / 分割照射 / 放射線治療生物学 / 放射線感受性 / 獲得放射線耐性 / side population / 臨床的放射線耐性 (CRR) / 放射線獲得耐性 (ARR) / 放射線がん治療 / 放射線抵抗性 / 放射線分割照射 |
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| Outline of Final Research Achievements |
We investigated the inducible radioresistant mechanism that cancer cells are able to proliferate under 2 Gy/day of fractionated radiation exposure, so called clinically-relevant radioresistant phenotype (CRR). For CRR formation, we revealed that pre-exposure with less than 2 Gy/day of fractionated dose and stepwise dose-escalation was critically required prior to 2 Gy/day of fractionated exposure. Pre-exposure with lower fractionated dose brought radioresistant phenotype (acquired radioresistance, ARR) and dose-escalation gradually enhanced radioresisntace. We also found that the nature of cancer stem cell or epithelial-mesenchymal transition, which is generally known as the factors contributing acquired radioresistance, was not involved in CRR formation. We also found less DNA damage, especially DNA double strand breaks, in radioresistant cells and that suppression of DNA-damage response might be involved in the mechanism of ARR and/or CRR formation.
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Guanine nucleotide-binding protein 1 is one of the key molecules contributing to cancer cell radioresistance.2014
Author(s)
Fukumoto M, Amanuma T, Kuwahara Y, Shimura T, Suzuki M, Mori S, Kumamoto H, Saito Y, Ohkubo Y, Duan Z, Sano K, Oguchi T, Kainuma K, Usami S, Kinoshita K, Lee I, Fukumoto M.
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Journal Title
Cancer Sci.
Volume: 105(10)
Pages: 1351-9
Related Report
Peer Reviewed
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