瘤基因诱导的Nrf2转录促进ROS排毒和瘤发生
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
概括
像Kras,Braf和Myc这样的瘤基因通过增加抗氧化剂Nrf2途径来抑制活性氧物种 (ROS),促进癌症的发展. 向Nrf2可以抑制瘤基因驱动的瘤生长.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 反应性氧物种 (ROS) 具有突变性,可以促进癌症.
- Nrf2 (核因子红色素2相关因子2) 途径调节抗氧化反应.
- 在新生病中观察到Nrf2激活的增加,这表明它有助于瘤的产生.
研究的目的:
- 研究瘤基因表达细胞中的ROS代谢.
- 确定瘤基因 (Kras,Braf,Myc) 在调节Nrf2通路中的作用.
- 探索在瘤发生过程中准Nrf2的治疗潜力.
主要方法:
- 利用了表达瘤基因Kras,Braf和Myc等位基因的初级小鼠细胞.
- 评估ROS水平和Nrf2转录.
- 在体内基因向Nrf2通路.
主要成果:
- 瘤基因克拉斯,布拉夫和迈克积极抑制ROS.
- 瘤基因增加了Nrf2转录,提高了基底抗氧化剂程序.
- 基因向Nrf2受损的K-Ras(G12D) 诱导的增殖和瘤发生.
结论:
- 瘤基因诱导的Nrf2激活是一种促进癌症的新机制.
- Nrf2抗氧化剂程序是以前未知的瘤发生的调解者.
- 向Nrf2可能是癌症治疗的可行策略.
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