Requirement for Rac1 in a K-ras-induced lung cancer in the mouse
Requirement for Rac1 in a K-ras-induced lung cancer in the mouse
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DOI：
10.1158/0008-5472.can-07-2300
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发表时间：
2007-09-01
期刊：
影响因子：
11.2
通讯作者：
Jacks, Tyler
中科院分区：
文献类型：
--
作者：
Kissil, Joseph L.;Walmsley, Marita J.;Jacks, Tyler
鉴于Ras突变在人类癌症中的普遍存在，了解致癌Ras导致转化的下游效应途径至关重要。为了直接评估在K-ras诱导的肿瘤发生中对Rac1的需求，我们采用了一种肺癌模型，其中K-ras的致癌等位基因可以在存在或不存在Rac1的条件缺失的情况下通过cre介导的重组激活。我们发现在这个模型中，Rac1功能是肿瘤发生所必需的。此外，虽然单独缺失Rac1与细胞活力和增殖是相容的，但当与原代上皮细胞中K-ras的激活结合时，缺失Rac1会导致细胞增殖的严重减少。这些数据表明，在表达致癌K-ras的细胞中，对Rac1功能有特定的要求。
Given the prevalence of Ras mutations in human cancer, it is critical to understand the effector pathways downstream of oncogenic Ras leading to transformation. To directly assess the requirement for Rac1 in K-ras-induced tumorigenesis, we employed a model of lung cancer in which an oncogenic allele of K-ras could be activated by Cre-mediated recombination in the presence or absence of conditional deletion of Rac1. We show that Rac1 function is required for tumorigenesis in this model. Furthermore, although Rac1 deletion alone was compatible with cell viability and proliferation, when combined with K-ras activation in primary epithelial cells, loss of Rac1 caused a profound reduction in proliferation. These data show a specific requirement for Rac1 function in cells expressing oncogenic K-ras.