肺腺癌における新規イレッサ耐性獲得メカニズムの解明

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Author: 中田, 飛鳥ほか

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Publication date: 2015-05-21

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Note (General)：: 金沢大学がん進展制御研究所イレッサ（ゲフィチニブ）はEGFRに変異をもつ肺腺癌の患者に対して奏功率が非常に高いが、数年以内に再発してしまうことが深刻な問題となっている。我々はイレッサ耐性のメカニズムを解明するために、肺腺癌由来PC9細胞からイレッサ耐性株PC9M2樹立した。このPC9M2細胞を解析し...

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Material Type: 文書・図像類
Title: 肺腺癌における新規イレッサ耐性獲得メカニズムの解明
Author/Editor: 中田, 飛鳥
Nakata, Asuka
Author Heading: 中田, 飛鳥
Nakata, Asuka
Publication Date: 2015-05-21
Publication Date (W3CDTF): 2015-05-21
Alternative Title: Novel molecular mechanisms of acquired resistance to gefitinib in lung adenocarcinoma
Periodical title: 平成26(2014)年度科学研究費補助金若手研究(B) 研究成果報告書 = 2014 Fiscal Year Final Research Report
No. or year of volume/issue: 2013-04-01 – 2015-03-31
Volume: 2013-04-01 – 2015-03-31
Pages: 4p.-
Text Language Code: jpn
Subject Heading: 肺腺癌
イレッサ
Target Audience: 一般
Note (General): 金沢大学がん進展制御研究所
イレッサ（ゲフィチニブ）はEGFRに変異をもつ肺腺癌の患者に対して奏功率が非常に高いが、数年以内に再発してしまうことが深刻な問題となっている。我々はイレッサ耐性のメカニズムを解明するために、肺腺癌由来PC9細胞からイレッサ耐性株PC9M2樹立した。このPC9M2細胞を解析した結果、βカテニンシグナルが亢進していることが分かり、βカテニンの活性阻害によってPC9M2株にイレッサ感受性が回復することを証明した。さらに肺腺癌患者の組織においても、βカテニンの活性が高い患者ではイレッサの感受性が低いことが明らかになり、βカテニンの活性がイレッサの感受性や獲得耐性に関与する可能性が示唆された。
Although Iressa (gefitinib) were greatly effective in lung adenocarcinoma patients harboring EGFR mutations, these patients ultimately have acquired resistance to gefitinib. To explore novel molecular mechanisms for gefitinib-resistance, we established the gefitinib-resistant PC9M2 cells that were spontaneously derived from gefitinib-sensitive PC9. Microarray analysis revealed that β－catenin-related genes were upregulated in PC9M2 cells compared with PC9 cells. We next demonstrated that the downregulation of β-catenin partially restored the sensitivity to gefitinib in PC9M2 cells. Using the tissues from lung cancer patients harbored EGFR mutation, we showed that activation of β-catenin was related with gefitinib sensitivity in patient’s samples, suggesting that enhanced β-catenin activation is associated with primary and acquired resistance to gefitinib. Targeting β-catenin pathway may be useful for overcoming the resistance to gefitinib.
研究課題/領域番号:25830111, 研究期間(年度):2013-04-01 – 2015-03-31
DOI: 10.24517/00059144
Access Restrictions: 限定公開
Related Material: https://kaken.nii.ac.jp/ja/search/?kw=70597921
https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-25830111/
https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-25830111/25830111seika/
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 金沢大学 : 金沢大学学術情報リポジトリKURA