Distinct requirements for Ras oncogenesis in human versus mouse cells
Distinct requirements for Ras oncogenesis in human versus mouse cells
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DOI：
10.1101/gad.993902
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发表时间：
2002-08-15
影响因子：
10.5
通讯作者：
Counter, CM
中科院分区：
文献类型：
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作者：
Hamad, NM;Elconin, JH;Counter, CM
与人类致癌Ras相关的肿瘤谱通常与用致癌物处理或工程化以零星表达致癌Ras的小鼠中的肿瘤谱不同，这表明Ras转化的机制在人类中可能不同。Ras主要刺激三种主要类型的效应蛋白，Rafs，PI 3-激酶和Ra 1GEFS，Raf通常在转化鼠细胞方面最有效。使用致癌的Ras突变体，激活单一的效应以及组成型活性效应，我们发现，Ra 1GEF，而不是Raf或PI 3-激酶途径，是足够的Ras在人类细胞中的转化。因此，致癌Ras可以通过不同的机制转化小鼠和人类细胞，而Ra 1GEF通路-以前被认为在Ras转化中起次要作用-可能代表抗癌治疗的新靶点。
The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector proteins, Rafs, PI3-kinase, and Ra1GEFS, with Raf generally being the most potent at transforming murine cells. Using oncogenic Ras mutants that activate single effectors as well as constitutively active effectors, we find that the Ra1GEF, and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in human cells. Thus, oncogenic Ras may transform murine and human cells by distinct mechanisms, and the Ra1GEF pathway-previously deemed to play a secondary role in Ras transformation-could represent a new target for anti-cancer therapy.