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Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells
http://hdl.handle.net/10069/35006
http://hdl.handle.net/10069/350068b85da5a-a7d5-4569-89d3-95e428724639
名前 / ファイル | ライセンス | アクション |
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CanSci105_1601.pdf (1.3 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2015-01-15 | |||||
タイトル | ||||||
タイトル | Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Adult T-cell leukemia-lymphoma | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | HSP90 inhibitors | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NF-κB | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | NVP-AUY922 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | PIM kinases | |||||
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 |
Taniguchi, Hiroaki
× Taniguchi, Hiroaki× Hasegawa, Hiroo× Sasaki, Daisuke× Ando, Koji× Sawayama, Yasushi× Imanishi, Daisuke× Taguchi, Jun× Imaizumi, Yoshitaka× Hata, Tomoko× Tsukasaki, Kunihiro× Uno, Naoki× Morinaga, Yoshitomo× Yanagihara, Katsunori× Miyazaki, Yasushi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. This report first describes the effectiveness of a novel HSP90 inhibitor NVP-AUY922 to adult T-cell leukemia-lymphoma (ATL) cells. | |||||
書誌情報 |
Cancer Science 巻 105, 号 12, p. 1601-1608, 発行日 2014-12-01 |
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出版者 | ||||||
出版者 | 日本癌学会 | |||||
出版者別言語 | ||||||
Japanese Cancer Association | ||||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13479032 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1111/cas.12540 | |||||
権利 | ||||||
権利情報 | c 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association. | |||||
権利 | ||||||
権利情報 | This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. | |||||
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 | Cancer Science, 105(12), pp.1601-1608; 2014 |