c-jun has multiple enhancing activities in the novel cross talk between the androgen receptor and Ets variant gene 1 in prostate cancer
c-jun has multiple enhancing activities in the novel cross talk between the androgen receptor and Ets variant gene 1 in prostate cancer
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DOI：
10.1158/1541-7786.mcr-06-0430
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发表时间：
2007-07-01
影响因子：
5.2
通讯作者：
Shemshedini, Lirim
中科院分区：
文献类型：
--
作者：
Cai, Changmeng;Hsieh, Chen-Lin;Shemshedini, Lirim
c-Jun的多重转录作用显示在雄激素受体（AR）与其新靶基因Ets变体基因1（ETV 1）之间的新型串扰中。在这份报告中，我们表明，c-Jun可以介导AR诱导ETV 1的表达独立的c-Jun反式激活功能。有趣的是，c-Jun可以反式激活克隆的ETV 1启动子，也在配体激活的AR的情况下，这表明c-Jun可以诱导ETV 1表达的两种机制。此外，野生型c-Jun和反式激活缺陷突变体都可以增强ETV 1的转录活性，如通过报告基因测定和基质金属蛋白酶基因（众所周知的Ets蛋白的靶基因）的内源性表达所测量的。c-Jun突变蛋白的过表达也导致前列腺癌细胞侵袭增加。免疫沉淀和免疫细胞化学实验显示c-Jun与AR或ETV 1共纯化和共定位，表明c-Jun通过物理缔合作用于AR或ETV 1。总的来说，这些结果，以及前列腺肿瘤中ETV 1，c-Jun和AR的平行过表达，意味着c-Jun在连接配体激活的AR与ETV 1表达升高的途径中起着关键作用，导致基质金属蛋白酶表达增强和前列腺癌细胞侵袭。
The multiple transcriptional roles of c-Jun are shown in a novel cross-talk between the androgen receptor (AR) and its new target gene, Ets variant gene 1 (ETV1). In this report, we show that c-Jun can mediate AR induction of ETV1 expression independent of c-Jun transactivation function. Interestingly, c-Jun can transactivate the cloned ETV1 promoter also in the absence of ligand-activated AR, suggesting two mechanisms by which c-Jun can induce ETV1 expression. In addition, both wild-type c-Jun and a transactivation-deficient mutant can enhance the transcriptional activity of ETV1, as measured by both reporter gene assay and endogenous expression of matrix metalloproteinase genes, well-known, targets of Ets proteins. Overexpression of the c-Jun mutant protein also led to increased prostate cancer cell invasion. Immunoprecipitation and immunocytochemistry experiments showed copurification and colocalization of c-Jun with AR or ETV1, suggesting that c-Jun acts on AR or ETV1 via a physical association. Collectively, these results, together with a parallel overexpression of ETV1, c-Jun, and AR in prostate tumors, imply that c-Jun plays a pivotal role in the pathway that connects ligand-activated AR to elevated ETV1 expression, leading to enhanced expression of matrix metalloproteinases and prostate cancer cell invasion.