Gastrin-cholecystokinin(B) Receptor Expression in AGS Cells is Associated with Direct Inhibition and Indirect Stimulation of Cell Proliferation Via Paracrine Activation of the Epidermal Growth Factor Receptor

Overview

Journal Gut

Specialty Gastroenterology

Date 2002 May 16

PMID 12010885

Citations 25

Authors

A Varro

P J Noble

L E Wroblewski

L Bishop

G J Dockray

Affiliations

Soon will be listed here.

Abstract

Background: Activation of the gastrin-cholecystokinin(B) (CCK(B)) receptor stimulates cell proliferation and increases production of ligands for the epidermal growth factor receptor (EGF-R).

Aims: To determine the role of gastrin-CCK(B) activation in stimulation of cell proliferation via paracrine activation of EGF-R.

Methods: AGS cells were transfected with the gastrin-CCK(B) receptor (AGS-G(R) cells) or with green fluorescent protein (AGS-GFP cells). Proliferation was determined by [(3)H] thymidine incorporation, flow cytometry, and cell counting.

Results: Gastrin inhibited proliferation of AGS-G(R) cells by delaying entry into S phase. However, when AGS-G(R) cells were cocultured with AGS-GFP cells, gastrin stimulated proliferation of the latter. Immunoneutralisation and pharmacological studies using metalloproteinase and kinase inhibitors indicated that the proliferative response was mediated by paracrine stimulation of EGF-R and activation of the mitogen activated protein kinase pathway through release of heparin binding EGF.

Conclusions: Gastrin can directly inhibit, and indirectly stimulate, proliferation of gastric AGS cells.

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