Mycの消去は,小腸のApc欠乏症を救済する
Owen J Sansom1, Valerie S Meniel, Vanesa Muncan
1The Beatson Institute, Garscube Estate, Glasgow G61 1BD, UK. o.sansom@beatson.gla.ac.uk
Nature
|March 23, 2007
まとめ
Mycの喪失は,Apc遺伝子の削除によって引き起こされた腸の異常を救出し,Mycが早期の結腸直腸がんの発症の重要な媒介者であることを明らかにしました. この発見は,APCの喪失後のWnt経路の活性化におけるMycの重要な役割を強調しています.
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:
- Adenomatous polyposis coli (APC) 遺伝子変異は,家族性アデノマトス型多重症 (FAP) と散発性結腸直腸がんの中心にある.
- APCの無活性化は,大腸がんにおける重要なイベントであるβ-カタニン-Tcf4転写複合体の構成的活性化につながる.
- プロトオンコゲンc-MYCはWnt経路の標的であるが,腸内でのAPC喪失後のその特定の役割は不明である.
研究 の 目的:
- Apc喪失後の腸内のMycの役割を調査する.
- MycがApcの消去に関連したフェノタイプを媒介するかどうかを判断する.
- Apc喪失後のWnt標的遺伝子の活性化におけるMycの機能を明らかにする.
主な方法:
- 大人のネズミの小腸におけるApcとMyc遺伝子の同時削除.
- 腸の分化,移動,増殖,アポトーシスのフェノタイプ分析.
- Wnt標的遺伝子の活性化を評価するために配列解析を用いた遺伝子発現プロファイリング.
主要な成果:
- Mycの喪失は,Apcの削除によって引き起こされた異常な分化,移動,増殖,およびアポトーシス現象型を救出しました.
- 核β-cateninの持続的に高いレベルにもかかわらず,救助が行われました.
- Mycは,APCの喪失後のほとんどのWnt標的遺伝子の活性化に不可欠であることが判明しました.
結論:
- Mycは,Apcの喪失後の腸内新形成の初期段階において,重要なメディエーターとして作用する.
- これらの発見は,Apc欠乏性大腸がんにおけるWnt経路の主要な下流効果因子としてMycを確立しています.
- Mycのターゲティングは,APC変異を有する大腸がんの治療戦略を提供することができる.
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