p53機能の回復は,体内で腫瘍の回帰につながります

Andrea Ventura¹, David G Kirsch, Margaret E McLaughlin

¹Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.

Nature

|January 26, 2007

まとめ

マウスのp53腫瘍抑制遺伝子の機能を回復させることで,既存のリンパ腫や肉腫が衰退した. これは,p53再活性化を標的とするのが有効ながん治療戦略である可能性があることを示唆しています.

科学分野:

腫瘍学腫瘍学
分子生物学は分子生物学である.
遺伝学遺伝学とは

背景:

腫瘍発生には,腫瘍遺伝子の活性化と腫瘍抑制遺伝子の不活性化が含まれます.
腫瘍が維持のために継続的な腫瘍遺伝子の発現を必要とする腫瘍遺伝子の依存症は,検証された治療目標です.
持続的な腫瘍抑制遺伝子の不活性化が腫瘍の維持に果たす役割は不明である.

研究の目的:

腫瘍抑制経路,特にp53の持続的な無活性化が,腫瘍の維持に必要なかどうかを調査する.
確立された癌の腫瘍抑制遺伝子を再活性化する治療の可能性を調査する.

主な方法:

Cre-loxPベースのシステムをマウスモデルにおける腫瘍抑制遺伝子発現の時間的制御に活用した.
腫瘍の回帰を研究するために,原発性リンパ腫と肉腫のマウスモデルを開発しました.

主要な成果:

固有のp53発現の回復は,マウスにおける既成リンパ腫と肉腫の回復につながった.
正常な組織はp53の回復によって影響を受けませんでした.
腫瘍の回帰メカニズムは,腫瘍のタイプによって異なる:リンパ腫のアポプトーシス,サルコマの老化による成長抑制.

結論:

すべての腫瘍の維持には,持続的なp53不活性化は必要ではありません.
p53の薬理学的再活性化は,ヒトがんの治療戦略として有望である.
p53の回復に対する腫瘍特異的な反応は,がん治療の複雑さを強調しています.

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