c-Jun NH(2)-末端激酶在 Ras 引发的肿瘤形成中的作用。
Requirement of c-Jun NH(2)-terminal kinase for Ras-initiated tumor formation.
机构信息
Howard Hughes Medical Institute, Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605, USA.
出版信息
Mol Cell Biol. 2011 Apr;31(7):1565-76. doi: 10.1128/MCB.01122-10. Epub 2011 Jan 31.
Abstract
The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway causes increased gene expression mediated, in part, by members of the activating transcription factor protein (AP1) group. JNK is therefore implicated in the regulation of cell growth and cancer. To test the role of JNK in Ras-induced tumor formation, we examined the effect of compound ablation of the ubiquitously expressed genes Jnk1 plus Jnk2. We report that JNK is required for Ras-induced transformation of p53-deficient primary cells in vitro. Moreover, JNK is required for lung tumor development caused by mutational activation of the endogenous KRas gene in vivo. Together, these data establish that JNK plays a key role in Ras-induced tumorigenesis.
摘要
c-Jun NH(2)-末端激酶（JNK）信号转导通路导致基因表达增加，部分原因是激活转录因子蛋白（AP1）家族的成员。因此，JNK 参与了细胞生长和癌症的调控。为了测试 JNK 在 Ras 诱导的肿瘤形成中的作用，我们研究了普遍表达的基因 Jnk1 和 Jnk2 同时缺失的影响。我们报告说，JNK 是 Ras 诱导的 p53 缺陷型原代细胞体外转化所必需的。此外，JNK 对于体内内源性 KRas 基因的突变激活引起的肺癌发展也是必需的。这些数据共同表明，JNK 在 Ras 诱导的肿瘤发生中发挥关键作用。
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