腫瘍遺伝子の誘発によるNrf2転写は,ROSの解毒と腫瘍発生を促進する
Gina M DeNicola1, Florian A Karreth, Timothy J Humpton
1Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
Nature
|July 8, 2011
まとめ
Kras,Braf,Mycのような腫瘍遺伝子は,抗酸化物質Nrf2経路を増加させ,がんの発症を促進することによって,活性酸素種 (ROS) を抑制します. Nrf2をターゲットにすることで,腫瘍原発性腫瘍の成長を抑制します.
科学分野:
- 細胞生物学 細胞生物学
- 腫瘍学 腫瘍学
- 分子生物学は分子生物学である.
背景:
- 反応性酸素種 (ROS) は変異性であり,がんを誘発する可能性があります.
- Nrf2 (Nuclear factor erythroid 2-related factor 2) 経路は,抗酸化反応を調節するものである.
- ネオプラジアではNrf2の活性化が増加することが観察され,これは腫瘍原性作用を示唆している.
研究 の 目的:
- 腫瘍遺伝子を発現する細胞におけるROSの代謝を調査する.
- Nrf2経路の調節における腫瘍遺伝子の (Kras, Braf, Myc) 役割を決定する.
- 腫瘍生成におけるNrf2を標的とした治療の可能性を調査する.
主な方法:
- 発がん性Kras,Braf,Mycアレルを発現する原発性ネズミの細胞を使用した.
- 評価されたROSレベルとNrf2転写.
- 遺伝子的にNrf2経路をターゲットにした in vivo.
主要な成果:
- 腫瘍遺伝子のクラス,ブラフ,マイクはROSを積極的に抑制した.
- 腫瘍遺伝子はNrf2の転写を増加させ,基礎的抗酸化プログラムを高めました.
- Nrf2の遺伝的ターゲティングは,K-Ras (((G12D)) 誘発の増殖と腫瘍発生を阻害しています.
結論:
- 腫瘍遺伝子の誘発によるNrf2活性化は,がんを促進する新しいメカニズムです.
- Nrf2の抗酸化プログラムは,これまで認識されていない腫瘍生成の媒介者です.
- Nrf2をターゲットにすることは,がん治療の有効な戦略かもしれません.
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