Article Text
Abstract
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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- 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
Footnotes
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↵* Present address: Department of Pathology, Lancaster Royal Infirmary, Lancaster, UK