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Gastrin-cholecystokininB 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
  1. A Varro,
  2. P J Noble,
  3. L E Wroblewski,
  4. L Bishop*,
  5. G J Dockray
  1. Physiological Laboratory, University of Liverpool, Liverpool UK
  1. Correspondence to:
    A Varro, Physiological Laboratory, University of Liverpool, Crown St, PO Box 147, Liverpool L69 3BX, UK;


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

Aims: To determine the role of gastrin-CCKB activation in stimulation of cell proliferation via paracrine activation of EGF-R.

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

Results: Gastrin inhibited proliferation of AGS-GR cells by delaying entry into S phase. However, when AGS-GR 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.

  • gastrin
  • proliferation
  • gastric epithelium
  • epidermal growth factor
  • cholecystokinin
  • AGS cells
  • CCK, cholecystokinin
  • ECL, enterochromaffin-like cell
  • EGF, epidermal growth factor
  • EGF-R, epidermal growth factor receptor
  • FBS, fetal bovine serum
  • GFP, green fluorescent protein
  • HB-EGF, heparin binding EGF
  • G17, heptadecapeptide gastrin
  • MAP, mitogen activated protein
  • PBS, phosphate buffered saline
  • PKC, protein kinase C
  • PMA, phorbol-12-myristate-13-acetate
  • TGF-α, transforming growth factor α

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  • * Present address: Department of Pathology, Lancaster Royal Infirmary, Lancaster, UK