title: EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells.
abstract: 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.
authors.affiliation: Department of Pathology, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Suo
authors.forename: Min
authors.initials: M
authors.lastname: Yan
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Fu
mesh_terms: D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017920:Antiporters / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D027963:Chloride-Bicarbonate Antiporters; D051766:Early Growth Response Protein 1 / Q000378:metabolism / Q000502:physiology*; D005755:Gastrins / Q000502:physiology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D043887:Receptor, Cholecystokinin B / Q000378:metabolism; D064606:SLC4A Proteins; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013274:Stomach Neoplasms; D015854:Up-Regulation
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D005755:Gastrins; D020033:Protein Isoforms; D043887:Receptor, Cholecystokinin B; D064606:SLC4A Proteins; C579496:SLC4A2 protein, human; D016329:Sp1 Transcription Factor