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.
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).


OBJECTIVE
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.
Varro
A
A
Physiological Laboratory, University of Liverpool, Liverpool, UK. avarro@liverpool.ac.uk
Noble
P J
PJ
Wroblewski
L E
LE
Bishop
L
L
Dockray
G J
GJ
D002455:Cell Division / Q000502:physiology; D004759:Enterochromaffin Cells / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D008164:Luminescent Proteins; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases; D013936:Thymidine