EGF receptor activation of the human gastrin gene: a tale of two zinc finger transcription factor families.

Gastrin is one of the oldest and most actively studied of the gastrointestinal peptides. Adult expression of the mature peptide is restricted to the stomach and duodenum. However, it is antral gastrin that is subject to feedback regulation from the counter-regulatory peptide somatostatin as a function of gastric pH. Yet little is known about the molecular steps required to modulate the synthesis of this peptide. Using cell culture models, a GC-rich regulatory element called gERE has been identified that binds two families of zinc finger transcription factors--Sp and ZBP. Competitive binding of these two transcription factor families in association with changes in their phosphorylation state appears to mediate the positive and negative activation of this gene in response to EGF receptor ligands. These findings contribute to our understanding of gastrin gene expression in the presence of the activated ras oncogene, e.g., during colonic transformation.