Gastrin induces heparin-binding epidermal growth factor-like growth factorin rat gastric epithelial cells transfected with gastrin receptor

Background & Aims: Parietal cells express heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), However, it is unknown whether HB -EGF mediates the trophic action of gastrin. The purpose of this study was to determine whether gastrin modulates the expression of HB-EGF, which medi ates the proliferative effects of gastrin on gastric epithelial cells. Meth ods: RGM1 cells, a rat gastric epithelial cell line, were transfected with a human gastrin receptor complementary DNA, Gastrin induction of messenger RNAs (mRNAs) for EGF-related polypeptides was assayed by Northern blotting. Processing of cell surface-associated proHB-EGF and secretion of HB-EGF we re determined by flow cytometry and Western blotting, respectively, Tyrosin e phosphorylation of the EGF receptor was assayed by immunoprecipitation an d Western blotting with an antiphosphotyrosine antibody. Cell growth was ev aluated by [H-3]thymidine incorporation. Results: Gastrin induced expressio n of HB-EGF mRNA, processing of proHB-EGF, release of HB-EGF into the mediu m, and tyrosine phosphorylation of the EGF receptor. The growth-stimulatory effects of gastrin were partly inhibited by anti-rat HB-EGF serum and comp letely blocked by AG1478, an EGF receptor-specific tyrphostin. Conclusions: The findings suggest that HB-EGF at least partially mediates the prolifera tive effects of gastrin on gastric epithelial cells.