EGF receptor activation stimulates endogenous gastrin gene expression in canine G cells and human gastric cell cultures

Michael G. Ford, John Del Valle, Carol J. Soroka, Juanita L. Merchant

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Gastrin release from the antral gastrin-expressing cell (G cell) is regulated by bombesin and luminal factors. Yet, these same extracellular regulators do not stimulate expression of the gene. Since the gastric mucosa expresses large quantities of EGF receptor ligands such as TGFα, we examined whether EGF receptor ligands stimulate gastrin gene expression in gastrin- expressing cell cultures. EGF receptor activation of primary cultures stimulated gastrin gene expression about twofold; whereas bombesin treatment of antral G cell cultures stimulated gastrin release but not gene expression. EGF and TGFα were weak stimulants of gastrin release. EGF receptor activation of AGS human gastric adenocarcinoma cell line stimulated gastrin gene expression nearly fourfold; and gastrin reporter constructs transfected into AGS cells were stimulated more than fourfold by EGF. EGF induction was conferred by the previously defined GC-rich gastrin EGF response element (gERE) element located at -68 to -53 bp upstream from the cap site since a mutation of the gERE element abolished both basal and EGF induction. Moreover, EGF treatment of AGS cells stimulated binding of the transcription factor Sp1 to this element. Collectively, these results demonstrate that gastrin gene expression and gastrin release are regulated by different signaling pathways: gene expression by EGF receptor activation and gastrin secretion by neuropeptides and luminal factors.

Original languageEnglish (US)
Pages (from-to)2762-2771
Number of pages10
JournalJournal of Clinical Investigation
Volume99
Issue number11
DOIs
StatePublished - Jun 1 1997
Externally publishedYes

Keywords

  • DNA element
  • Gene expression
  • Gere
  • Sp1
  • TGF

ASJC Scopus subject areas

  • Medicine(all)

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