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Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells.
http://hdl.handle.net/10069/23199
http://hdl.handle.net/10069/23199f5c39fd7-1b46-4532-b2d9-5edb5fdd4fb6
名前 / ファイル | ライセンス | アクション |
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Leukemia23_2090.pdf (780.8 kB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2010-06-14 | |||||
タイトル | ||||||
タイトル | Activation of p53 by Nutlin-3a, an antagonist of MDM2, induces apoptosis and cellular senescence in adult T-cell leukemia cells. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | p53 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | senescence | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | apoptosis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | p14ARF | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | adult T-cell leukemia | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Nutlin | |||||
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 |
Hasegawa, Hiroo
× Hasegawa, Hiroo× Yamada, Yasuaki× Iha, Hidekatsu× Tsukasaki, Kunihiro× Nagai, Kazuhiro× Atogami, Sunao× Sugahara, Kazuyuki× Tsuruda, Kazuto× Ishizaki, Akiko× Kamihira, Shimeru |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | It has been reported that the induction of cellular senescence through p53 activation is an effective strategy in tumor regression. Unfortunately, however, tumors including adult T-cell leukemia/lymphoma (ATL) have disadvantages such as p53 mutations and a lack of p16(INK4a) and/or p14(ARF). In this study we characterized Nutlin-3a-induced cell death in 16 leukemia/lymphoma cell lines. Eight cell lines, including six ATL-related cell lines, had wild-type p53 and Nutlin-3a-activated p53, and the cell lines underwent apoptosis or cell-cycle arrest, whereas eight cell lines with mutated p53 were resistant. Interestingly, senescence-associated-beta-galactosidase (SA-beta-gal) staining revealed that only ATL-related cell lines with wild-type p53 showed cellular senescence, although they lack both p16(INK4a) and p14(ARF). These results indicate that cellular senescence is an important event in p53-dependent cell death in ATL cells and is inducible without p16(INK4a) and p14(ARF). Furthermore, knockdown of Tp53-induced glycolysis and apoptosis regulator (TIGAR), a novel target gene of p53, by small interfering RNA(siRNA) indicated its important role in the induction of cellular senescence. As many patients with ATL carry wild-type p53, our study suggests that p53 activation by Nutlin-3a is a promising strategy in ATL. We also found synergism with a combination of Nutlin-3a and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), suggesting the application of Nutlin-3a-based therapy to be broader than expected.Leukemia advance online publication, 27 August 2009; doi:10.1038/leu.2009.171. | |||||
書誌情報 |
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 巻 23, 号 11, p. 2090-2101, 発行日 2009-11 |
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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 | 08876924 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 14765551 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10668706 | |||||
PubMed番号 | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | PMID | |||||
関連識別子 | 19710698 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/leu.2009.171 | |||||
権利 | ||||||
権利情報 | c 2009 Nature Publishing Group | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Leukemia, 23(11), pp.2090?2101; 2009 |