Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism

Natalie F. Sinclair, Wandong Ai, Raktima Raychowdhury, Meixia Bi, Timothy C. Wang, Theodore J. Koh, John T. McLaughlin

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Gastrin is a known growth/differentiation factor for the gastric mucosa. Its effects are likely mediated by the induction of heparin-binding epidermal-like growth factor (HB-EGF), a member of the EGF family of growth factors that is expressed by gastric parietal cells. In this study, we investigated the regulation of the HB-EGF promoter by gastrin in a human gastric cancer cell line. Serial human HB-EGF promoter-luciferase reporter deletion constructs and heterologous promoter constructs were transfected into AGS-E cells and stimulated with gastrin (10-7 M) with or without various signal transduction inhibitors. EMSA were also performed. Gastrin stimulation resulted in a fivefold increase in HB-EGF-luciferase activity. The cis-acting element mediating gastrin responsiveness was mapped to the -69 to -58 region of the HB-EGF promoter. Gastrin stimulation was PKC dependent and at least partially mediated by activation of the EGF receptor.
    Original languageEnglish
    Pages (from-to)G992-G999
    JournalAJP: Gastrointestinal and Liver Physiology
    Volume286
    Issue number6
    DOIs
    Publication statusPublished - Jun 2004

    Keywords

    • Gastrointestinal mucosa
    • Peptide hormone

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