ID | 53004 |
フルテキストURL | |
著者 |
Ochi, Nobuaki
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Takigawa, Nagio
Kawasaki Hosp, Kawasaki Med Sch, Dept Gen Internal Med 4
Harada, Daijiro
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Yasugi, Masayuki
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Ichihara, Eiki
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Hotta, Katsuyuki
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Kaken ID
publons
researchmap
Tabata, Masahiro
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Kaken ID
researchmap
Tanimoto, Mitsune
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
Kaken ID
publons
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抄録 | To study epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance mechanisms, we established a novel gefitinib-resistant lung cancer cell line derived from an EGFR-mutant non-small cell lung cancer cell line (PC-9) pretreated with 4-(methylnitrosamino)1-(3-pyridy1)-1-butanone (designated PC9-GR). We found that gefitinib substantially suppressed the EGFR signaling pathway, whereas ERK was reactivated after several hours in PC9-GR but not in PC-9. The combination of gefitinib with ERK inhibition (by U0126) restored gefitinib susceptibility in PC9-GR, but PI3K-Akt inhibition with LY294002 did not. Although the levels of phosphorylated Src were up-regulated simultaneously with ERK reactivation, neither ERK suppression using U0126 nor an ERK-specific siRNA induced Src phosphorylation. Furthermore, dual inhibition of EGFR and Src restored gefitinib sensitivity in PC9-GR in vitro and in vivo. In conclusion, our results indicate that Src-mediated ERK reactivation may play a role in a novel gefitinib resistance mechanism, and that the combined use of gefitinib with a Src inhibitor may be a potent strategy to overcome this resistance.
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キーワード | EGFR
Src
ERK
Lung cancer
Gefitinib
Resistance
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発行日 | 2014-03-10
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出版物タイトル |
Experimental Cell Research
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巻 | 322巻
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号 | 1号
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開始ページ | 168
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終了ページ | 177
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ISSN | 0014-4827
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資料タイプ |
学術雑誌論文
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52960
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言語 |
英語
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著作権者 | (c) 2014 Elsevier Inc. All rights reserved.
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |