ETS1 lowers capillary endothelial cell density at confluence and induces the expression of VE-cadherin
ETS1 lowers capillary endothelial cell density at confluence and induces the expression of VE-cadherin
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DOI：
10.1038/sj.onc.1203563
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发表时间：
2000-05-11
期刊：
影响因子：
8
通讯作者：
Soncin, F
中科院分区：
文献类型：
--
作者：
Lelièvre, E;Mattot, V;Soncin, F
Ets 1是一种在血管生成过程中表达于内皮细胞的转录因子，但其靶基因和在血管形成中的功能尚不清楚。我们使用逆转录病毒载体在脑毛细血管内皮细胞和3 T3成纤维细胞中过度表达Ets 1作为标记蛋白。在内皮细胞汇合处，Ets 1的过表达减少了近一半的细胞密度，但成纤维细胞没有。由于汇合处的密度部分地由钙粘蛋白控制，这种生长停滞可能是由于这些细胞接触分子的上调。事实上，Ets 1增加了内皮特异性VE-钙粘蛋白的表达，而不影响N-钙粘蛋白的表达水平。同时，Ets成员的显性负突变体和Ets 1反义寡核苷酸抑制内皮细胞中VE-钙粘蛋白的表达，Ets 1结合到位于VE-钙粘蛋白启动子近端区域的两个Ets结合位点。这些位点的突变废除了Ets 1诱导的启动子反式激活。目前的工作是第一次演示的功能Ets 1在一个特定的内皮标志物的基础上，其内源性基因和蛋白质表达的调节。
Ets1 is a transcription factor expressed in endothelial cells during angiogenesis but its target genes and function in blood vessel formation are still unknown. We have over-expressed Ets1 as a tagged protein in brain capillary endothelial cells and in 3T3 fibroblasts using a retroviral vector. Over-expression of Ets1 reduced by nearly half cell density at confluence of endothelials but not of fibroblasts, As density at confluence is controlled in part by cadherins, this growth arrest could be due to the up-regulation of these cell contact molecules. Indeed, Ets1 increased the expression of the endothelial-specific VE-cadherin without affecting N-cadherin expression levels. In parallel, both dominant negative mutant of Ets members and an Ets1 anti-sense oligonucleotide inhibited VE-cadherin expression in endothelial cells, Ets1 bound to two Ets-binding sites located in the proximal region of the VE-cadherin promoter. Mutation of these sites abolished Ets1-induced transactivation of the promoter. The present work is the first demonstration of a function of Ets1 in the regulation of a specific endothelial marker based on its endogenous gene and protein expression.