EGR 1 is critical for gastrin‐dependent upregulation of anion exchanger 2 in gastric cancer cells

The essential anion exchanger ( AE ) involved in bicarbonate secretion is AE 2/ SLC 4 A 2, a membrane protein recognized to be relevant for the regulation of the intracellular p H in several cell types. Here we report that gastrin, a major gastrointestinal hormone, upregulates the expression of AE2 m RNA and protein in a cholecystokinin B receptor dependent manner in gastric cancer cells. The upregulated species of AE 2 m RNA originates from the classical upstream promoter of the AE 2 gene (here referred to as AE 2a1) which provides the binding site for transcription factors early growth response 1 ( EGR 1) and SP 1. EGR 1 upregulated the AE 2 expression that can be competitively inhibited by SP 1 in co‐transfection experiments. This competitive inhibition was avoided in cells because the SP 1 expression was time‐staggered to EGR 1 in response to gastrin. Overexpression or knockdown of EGR 1 consistently increased or decreased the expression of AE 2. Our data linked a novel signal pathway involved in gastrin‐stimulated AE 2 expression.