RASSF1A suppresses the c-Jun-NH2-kinase pathway and inhibits cell cycle progression
RASSF1A suppresses the c-Jun-NH2-kinase pathway and inhibits cell cycle progression
复制标题
DOI：
10.1158/0008-5472.can-04-2792
复制
发表时间：
2005-05-01
期刊：
影响因子：
11.2
通讯作者：
Yoo, DY
中科院分区：
文献类型：
--
作者：
Whang, YM;Kim, YH;Yoo, DY
一些癌基因，如激活的RAS，会导致肺细胞的恶性转化。C-Jun-NH2-Kinase(JNK)的激活对于这些细胞的致癌功能是必不可少的。在这项研究中，我们发现RASSF1A通过阻断JNK通路来抑制肺癌细胞的生长。外源表达的RASSF1A抑制JNIK的磷酸化，稳定表达RASSF1A的细胞JNK和c-jun的磷酸化水平降低，Cyclin D1下调。体外激酶分析表明，外源表达的RASSF1A抑制JNK活性，RASSF1A siRNA处理可恢复异位表达的JNK活性抑制。根据我们的数据，我们认为RASSF1A通过阻断癌基因介导的JNK在肺细胞中的激活而发挥抑制肿瘤的作用。
Some oncogenes, such as activated Ras, cause the malignant transformation of lung cells. c-jun-NH2-kinase (JNK) activation is essential for the oncogenic function of these cells. In this study, we show that RASSF1A inhibits the growth of lung cancer cells by blocking the JNK pathway. The exogenous expression of RASSF1A suppressed JNIK phosphorylation, and cells stably transfected with RASSF1A showed reduced JNK and c-Jun phosphorylation and Cyclin D1 down-regulation. An in vitro kinase assay showed that the exogenous expression of RASSF1A inhibited JNK activity and that JNK activity suppression due to ectopically expressed RASSF1A was revived by RASSF1A siRNA treatment. Based on our data, we suggest that RASSF1A exerts a tumor-suppressing effect by blocking oncogene-mediated JNK activation in lung cells.