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Involvement of decreased hypoxia-inducible factor 1 activity and resultant G1–S cell cycle transition in radioresistance of perinecrotic tumor cells
http://hdl.handle.net/10069/32591
http://hdl.handle.net/10069/3259124a74d7a-619f-48c3-9152-c8cbc4a06272
名前 / ファイル | ライセンス | アクション |
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Onco32_2058.pdf (3.8 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2013-07-03 | |||||
タイトル | ||||||
タイトル | Involvement of decreased hypoxia-inducible factor 1 activity and resultant G1–S cell cycle transition in radioresistance of perinecrotic tumor cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | hypoxia | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | hypoxia-inducible factor 1 (HIF-1) | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | radiation therapy | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | radioresistance | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | tumor microenvironments | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Zhu, Yuxi
× Zhu, Yuxi× Zhao, Tao× Itasaka, Satoshi× Zeng, LiHua× Yeom, ChanJoo× Hirota, K× Suzuki, Keiji× Morinibu, Akiyo× Shinomiya, Kazumi× Ou, Guangfei× Yoshimura, M× Hiraoka, Masahiro× Harada, H |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Cancer patients often suffer from local tumor recurrence after radiation therapy. Some intracellular and extracellular factors, such as activity of hypoxia-inducible factor 1 (HIF-1), cell cycle status and oxygen availability, have been suggested to affect DNA damage responses and eventual radioresistant characteristics of cancer cells. But when, where, and how these factors affect one another and induce cellular radioresistance is largely unknown. Here, we analyzed mechanistic and spatio-temporal relationships among them in highly heterogeneous tumor microenvironments. Experiments in vitro demonstrated that a decrease in the glucose concentration reduced the transcriptional activity of HIF-1 and expression of a downstream gene for the cell cycle regulator p27 Kip1 even under hypoxic conditions. Then, the proportion of cells in the radioresistant S phase increased, whereas that in the radiosensitive G 1 phase decreased, significantly. Immunohistochemical analyses showed that cancer cells in perinecrotic hypoxic regions, which should be under low-glucose conditions, expressed little HIF-1α, and therefore, were mainly in S phase and less damaged by radiation treatment. Continuous administration of glucagon, which increases the blood glucose concentration and so improves glucose availability in perinecrotic hypoxic regions, induced HIF-1α expression and increased radiation-induced DNA damage. Taken all together, these results indicate that cancer cells in perinecrotic regions, which would be under low-glucose and hypoxic conditions, obtain radioresistance by decreasing the level of both HIF-1 activity and p27 Kip1 expression, and adjusting their cell cycle to the radioresistant S phase. | |||||
書誌情報 |
Oncogene 巻 32, 号 16, p. 2058-2068, 発行日 2013-04-18 |
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出版者 | ||||||
出版者 | Nature Publishing Group | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 09509232 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14765594 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/onc.2012.223 | |||||
権利 | ||||||
権利情報 | © 2013 Macmillan Publishers Limited All rights reserved. | |||||
権利 | ||||||
権利情報 | This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Oncogene, 32(16), pp.2058-2068; 2013 |