RaIGDS is required for tumor formation in a model of skin carcinoigenesis
RaIGDS is required for tumor formation in a model of skin carcinoigenesis
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DOI：
10.1016/j.ccr.2005.01.029
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发表时间：
2005-03-01
期刊：
影响因子：
50.3
通讯作者：
Marshall, CJ
中科院分区：
文献类型：
--
作者：
González-García, A;Pritchard, CA;Marshall, CJ
为了研究小GTdR ai的信号传导作用，我们产生了RaIGDS缺陷的小鼠，RaIGDS是一种激活Rai的鸟嘌呤核苷酸交换因子。我们发现RaIGDS对小鼠的发育是不利的，但在Ras诱导的肿瘤发生中起着重要作用。RaIGDS的缺乏导致肿瘤发生率、大小和多阶段皮肤癌发生中向恶性进展的减少，以及组织培养中Ras的转化减少。RaIGDS似乎不参与细胞增殖的调节，而是控制转化细胞的存活。在从皮肤肿瘤分离的细胞中进行的实验表明RaIGDS通过激活JNK/SAPK途径介导细胞存活。这些研究将RaIGDS确定为体内Ras依赖性致癌作用的关键组分。
To investigate the role of signaling by the small GTPase Rai, we have generated mice deficient for RaIGDS, a guanine nucleotide exchange factor that activates Rai. We show that RaIGDS is dispensable for mouse development but plays a substantial role in Ras-induced oncogenesis. Lack of RaIGDS results in reduced tumor incidence, size, and progression to malignancy in multistage skin carcinogenesis, and reduced transformation by Ras in tissue culture. RaIGDS does not appear to participate in the regulation of cell proliferation, but instead controls survival of transformed cells. Experiments performed in cells isolated from skin tumors suggest that RaIGDS mediates cell survival through the activation of the JNK/SAPK pathway. These studies identify RaIGDS as a key component in Ras-dependent carcinogenesis in vivo.