EGR1 is critical for gastrin-dependent upregulation of anion exchanger 2 in gastric cancer cells

Authors

  • Ting Wang,

    1. 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, China
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    • *These authors contributed equally to this work
  • Lei Zhao,

    1. 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, China
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    • *These authors contributed equally to this work
  • Ye Yang,

    1. Department of Digestive Medicine, Lishui Hospital, Zhejiang, China
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  • Hua Tian,

    1. 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, China
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  • Wen-Hao Suo,

    1. 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, China
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  • Min Yan,

    1. Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China
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  • Guo-Hui Fu

    Corresponding author
    • 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, China
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Correspondence

G.-H. Fu, Department of Pathology, Shanghai Jiao Tong University School of Medicine, No. 280, South Chong-Qing Road, Shanghai 200025, China

Fax: 86 21 6384 6590 776420

Tel: 86 21 6384 6590 ext. 776601

E-mail: fuguhu@263.net

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.

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