ネズミのp27Kip1遺伝子は,腫瘍抑制のためにハプロ不十分である
M L Fero1, E Randel, K E Gurley
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Nature
|November 21, 1998
まとめ
細胞増殖阻害剤であるp27タンパク質は,マウスの腫瘍抑制剤として作用する. 機能的なコピーを1つ持っていても,マウスは腫瘍に罹患しやすいので,p27を示しています.
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:
- p27Kipは,サイクリン依存キナーゼと細胞増殖を抑制するヒト腫瘍抑制タンパク質候補です.
- ヒトがんにおけるp27タンパク質の低レベルは,攻撃性と死亡率と相関しています.
- p27と腫瘍抑制の間の因果関係は,希少な同同位体の不活性化変異により不明である.
研究 の 目的:
- 腫瘍抑制におけるp27の役割を in vivoで調査する.
- p27がマウスの腫瘍抑制剤として機能するかどうかを判断する.
- ハプロ欠乏症を含むp27媒介による腫瘍抑制のメカニズムを探求する.
主な方法:
- ガンマ放射線と化学的発がん物質によるp27無糖性および異糖性マウスの生成と挑戦.
- p27欠乏マウスにおける腫瘍発達の分析.
- 残りの野生型アレルを評価するために,p27ヘテロジゴスマウスからの腫瘍の分子解析を行う.
主要な成果:
- p27 ヌリジゴス・ヘテロジゴス・マウスは,発癌物質に曝露した後の複数の組織で腫瘍の発生傾向を示した.
- p27はマウスの多重組織腫瘍抑制剤として機能する.
- 分子解析により,残った野生型p27アレルは,異合性マウスの腫瘍で変異または静止されていないことが判明し,ハプロ不十分性を示した.
結論:
- p27はマウスのハッポ不十分な腫瘍抑制剤であり,リセシブ腫瘍抑制遺伝子の伝統的な見解に異議を唱える.
- この発見は,腫瘍抑制遺伝子を評価する際にハプロ欠乏症を考慮すべきことを示唆している.
- 腫瘍抑制におけるp27の役割はin vivoで確認されており,ヒトの癌発達の理解に意味があります.
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