ETV1是一种谱系生存因子,在胃肠道 stromal 瘤中与 KIT 合作
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nature
|October 8, 2010
概括
胃肠道 stromal 瘤 (GIST) 来自高ETV1表达的Cajal (ICCs) 间歇性细胞. 激活KIT突变与ETV1合作,驱动瘤性ETS转录程序,促进GIST的发展.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 胃肠道 stromal 瘤 (GIST) 是人类最常见的肉瘤.
- GIST的特征是激活KIT或PDGFRA受体氨酸激酶中的突变.
- 卡哈尔的间歇细胞 (ICCs) 是GIST.的原始细胞.
研究的目的:
- 研究ETV1在GIST发育和瘤发生中的作用.
- 在GIST中确定ETV1,ICC和KIT突变之间的关系.
- 阐明在GIST中瘤转录因子激活的机制.
主要方法:
- 在ICC亚型和GIST样本中分析ETV1表达.
- 对ICC发展和GIST细胞系生长的ETV1要求的评估.
- 对ETV1结合部位的转录组分析和分析.
- 调查被激活的KIT对ETV1的监管.
主要成果:
- 在KIT敏感的ICC中,ETV1的表达很高,对其发展至关重要.
- ETV1在GIST中普遍表达,对于对伊马替尼布敏感和耐药GIST细胞系的生长至关重要.
- ETV1作为ICC-GIST特有的转录网络的主调节器,主要通过增强器结合.
- 激活的KIT延长了ETV1蛋白的稳定性,并与ETV1在瘤发生过程中合作.
结论:
- GIST来源于具有高内源ETV1表达的ICC.
- 激活KIT突变,结合高ETV1水平,启动一个致癌的ETS转录程序驱动GIST.
- 这项研究揭示了GIST中瘤转录因子激活的新机制,与其他依赖ETS的瘤不同.
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