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

被引:53
作者
Varro, A [1 ]
Noble, PJ [1 ]
Wroblewski, LE [1 ]
Bishop, L [1 ]
Dockray, GJ [1 ]
机构
[1] Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England
关键词
D O I
10.1136/gut.50.6.827
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background: Activation of the gastrin-cholecystokinin, (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-G(R) cells) or with green fluorescent protein (AGS-GFP cells). Proliferation was determined by [H-3] 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 EGFR 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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页码:827 / 833
页数:7
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