EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells
EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells
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EGR1 对于胃癌细胞中胃泌素依赖性阴离子交换剂 2 的上调至关重要。
DOI：
10.1111/febs.12058
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发表时间：
2013-01-01
期刊：
影响因子：
5.4
通讯作者：
Fu, Guo-Hui
中科院分区：
文献类型：
--
作者：
Wang, Ting;Zhao, Lei;Fu, Guo-Hui
参与碳酸氢盐分泌的必需阴离子交换剂（AE）是AE2/SLC4A2，这是一种被认为与几种细胞类型的细胞内pH调节有关的膜蛋白。在这里，我们报道了胃泌素，一种主要的胃肠激素，在胃癌细胞中以胆囊收缩素B受体依赖的方式上调AE2 mRNA和蛋白的表达。AE2 mRNA的上调种源于AE2基因的经典上游启动子（这里简称AE2a1），该启动子为转录因子早期生长反应1 （EGR1）和SP1提供结合位点。在共转染实验中，EGR1上调了SP1竞争性抑制的AE2表达。这种竞争性抑制在细胞中是避免的，因为SP1在响应胃泌素时与EGR1的表达是时间交错的。过表达或低表达EGR1均可增加或降低AE2的表达。我们的数据与胃泌素刺激的AE2表达相关的一个新的信号通路相关联。
The essential anion exchanger (AE) involved in bicarbonate secretion is AE2/SLC4A2, a membrane protein recognized to be relevant for the regulation of the intracellular pH in several cell types. Here we report that gastrin, a major gastrointestinal hormone, upregulates the expression of AE2 mRNA and protein in a cholecystokinin B receptor dependent manner in gastric cancer cells. The upregulated species of AE2 mRNA originates from the classical upstream promoter of the AE2 gene (here referred to as AE2a1) which provides the binding site for transcription factors early growth response 1 (EGR1) and SP1. EGR1 upregulated the AE2 expression that can be competitively inhibited by SP1 in co-transfection experiments. This competitive inhibition was avoided in cells because the SP1 expression was time-staggered to EGR1 in response to gastrin. Overexpression or knockdown of EGR1 consistently increased or decreased the expression of AE2. Our data linked a novel signal pathway involved in gastrin-stimulated AE2 expression.