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Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells.


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タイトル: Blockade of constitutively activated ERK signaling enhances cytotoxicity of microtubule-destabilizing agents in tumor cells.
著者: Tanimura, Susumu / Uchiyama, Aya / Watanabe, Kazushi / Yasunaga, Masahiro / Inada, Yoshiyuki / Kawabata, Takumi / Iwashita, Ken-Ichi / Noda, Sinji / Ozaki, Kei-Ichi / Kohno, Michiaki
発行日: 2009年 1月16日
出版者: Elsevier
引用: Biochemical and biophysical research communications, 378(3), pp.650-655; 2009
抄録: The extracellular signal-regulated kinase (ERK) signaling pathway is constitutively activated in many human tumor cell types. Given the cytoprotective role of this pathway, we examined whether its specific blockade might sensitize human tumor cells to the induction of apoptosis by various anticancer drugs. Although blockade of ERK signaling alone did not induce substantial cell death, it resulted in marked and selective enhancement of the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the ERK pathway is constitutively activated. The synergistic activation of c-Jun NH(2)-terminal kinase by the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent appeared to be responsible, at least in part, for this effect. These results suggest that administration of the combination of an ERK pathway inhibitor and a microtubule-destabilizing agent is a potential chemotherapeutic strategy for the treatment of tumor cells with constitutive activation of the ERK pathway.
キーワード: Apoptosis / Combination therapy / JNK / MEK inhibitor / Microtubule-destabilizing agent
URI: http://hdl.handle.net/10069/22250
ISSN: 0006291X
DOI: 10.1016/j.bbrc.2008.11.109
PubMed ID: 19059207
権利: Copyright © 2008 Elsevier Inc. All rights reserved.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:050 学術雑誌論文

引用URI : http://hdl.handle.net/10069/22250

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