腫瘍抑制剤PTENによるPKB/Akt依存細胞生存の負の調節
V Stambolic1, A Suzuki, J L de la Pompa
1Amgen Institute, and Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Cell
|October 20, 1998
まとめ
PTENは,細胞生存を調節することにより,腫瘍抑制剤として作用します. この研究は,PTENがPI3を否定的に調節することを示しています.
科学分野:
- 分子生物学は分子生物学である.
- 腫瘍学 腫瘍学
- 細胞生物学 細胞生物学
背景:
- PTEN (ホモログのフォスファタゼとテンシン) は,腫瘍抑制剤として知られています.
- タンパク質チロシン・フォスファタゼとテンシンとの同質性は,細胞の調節における役割を示唆している.
- 細胞増殖と生存経路の調節不良は,がんの特徴です.
研究 の 目的:
- PTENの細胞増殖とアポトーシスの制御における役割を調査する.
- PTENが腫瘍抑制剤として機能する分子機構を解明する.
- PTENとPI3K/Aktシグナル伝達経路の関係を検証する.
主な方法:
- 利用されたmPTEN変異マウス胚と不死化したマウス胚性線維芽細胞.
- 細胞増殖とアポトーシスに対する感受性を評価した.
- 測定されたタンパク質キナーゼB/Akt (PKB/Akt) 活性とリン酸化.
- in vitroでフォスファディチルイノシトール (3,4,5) トリスホスファートに対するPTENの酵素活性を調べた.
主要な成果:
- mPTEN変異胚は増殖を示した.
- mPTEN欠乏細胞は,アポトーシスの感受性の低下とPKB/Aktの活性度の上昇を示した.
- 外因的なPTEN発現により,アポトーシスの感受性が回復し,PKB/Aktのリン酸化が正常化しました.
- PTENは細胞内フォスファディチルニノシトール (3,4,5) トリスフォスファートレベルを陰性的に調節し,それを in vitro で脱酸化することが示されました.
結論:
- PTENは,腫瘍形成を抑制する上で重要な役割を果たします.
- PTENは,PI3K/PKB/Aktシグナル伝達経路を否定的に調節することによって,腫瘍抑制機能を果たします.
- この経路は,細胞の生存と増殖を制御するために極めて重要です.
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