一种不活跃的Braf激酶突变诱导肺腺癌
Patricia Nieto1, Chiara Ambrogio1, Laura Esteban-Burgos1
1Experimental Oncology, Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Nature
|August 8, 2017
概括
不活化的BRAF突变通过改变MAPK信号来启动肺腺癌. 野生型BRAF对瘤生长至关重要,
科学领域:
- 癌症学
- 分子生物学
- 癌症遗传学
背景情况:
- 肺腺癌的发病因子往往是未知的,阻碍了向治疗的发展.
- 与其他癌症中常见的激活突变不同,非激活的BRAF突变在肺癌中普遍存在.
研究的目的:
- 研究BRAF失活突变在肺癌发生过程中的作用.
- 探索BRAF,KRAS和MAPK信号在肺腺癌发育和进展中的相互作用.
主要方法:
- 在体内表达不活性Braf (D631A) 和Kras (G12V) 突变的小鼠模型.
- 对瘤发病,进展和细胞类型分化的分析.
- 药理上抑制MEK (Mek) 来调节MAPK的信号传递.
主要成果:
- 在小鼠中,表达非活性激酶Braf (D631A) 引发肺腺癌.
- 克拉斯 (G12V) 和布拉夫 (D631A) 的同时表达通过克拉夫激酶加速了瘤的启动和进展.
- 野生型Braf的切除会增加MAPK信号和瘤毒性,但也会诱导球状细胞转基因分化和致死性病变.
结论:
- 在肺癌中,BRAF 失活突变是引发事件的原因.
- MAPK通路的信号强度决定了瘤的表型和细胞起源.
- 针对BRAF和了解MAPK通路动态对于肺腺癌治疗至关重要.
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