多剤耐性ヒト肺がん細胞系におけるトランスポーター遺伝子の過剰発現
S P Cole1, G Bhardwaj, J H Gerlach
1Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Science (New York, N.Y.)
|December 4, 1992
まとめ
化学療法に耐性のある肺がん細胞は,新しいATP結合カセットトランスポーターを過剰に発現する. 染色体16の遺伝子増幅は,この過剰表現と薬剤耐性と相関し,新しい治療標的を提供している.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝学 遺伝学とは
- がん研究 がん研究
背景:
- ドクソルビシンで選択されたH69AR肺がん細胞は,複数の化学療法剤に耐性を示します.
- この耐性は,一般的な多剤耐性トランスポーターであるP-グリコタンパク質によって媒介されません.
- 新しい耐性メカニズムを理解することは,効果的な肺がん治療法の開発に不可欠です.
研究 の 目的:
- 肺がんにおける多剤耐性を与える新しい遺伝子とメカニズムを特定し,特徴づけること.
- H69AR細胞系における薬剤耐性の遺伝的基礎を調査する.
主な方法:
- H69AR細胞における過剰発現したメッセンジャーRNA (mRNA) に対応する補完的なDNA (cDNA) クローンの分離.
- ハイブリダイゼーション技術を用いたmRNA発現レベルの分析.
- 染色体マッピングによる遺伝子増幅分析 (染色体16 帯 p13.1).
- 遺伝子増幅とmRNA発現と薬物感受性の相関.
主要な成果:
- 新しいmRNA (7.88.2 kilobases) は,親のH69細胞と比較して,H69AR細胞で100〜200倍過剰発現していることが判明しました.
- この過剰発現は,染色体16のバンドp13.1.1.の同類遺伝子の増幅と関連していた.
- 薬剤感受性の回復は,mRNA発現の低下と遺伝子増幅の喪失と相関する.
- 特定されたmRNAは,ATP結合カセット (ABC) トランスメブラントランスポータースーパーファミリーのメンバーをコードする.
結論:
- 染色体16の遺伝子増幅により過剰発現する新しいATP結合カセットトランスポーターは,肺がんにおける多剤耐性を促進する.
- この発見は,肺がんにおける化学療法耐性を克服するための新しい分子標的を提供します.
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