Zinc ions mediate gastrin expression, proliferation, and migration downstream of the cholecystokinin-2 receptor

Abstract

Gastrin, acting via the cholecystokinin-2 receptor (CCK2R), activates its own promoter in a positivefeed-forward loop that may result in hypergastrinemia. Activity of the gastrin promoter is also stimulated by exogenous Zn2β ions. Here, the role of intracellular zinc and calcium signaling in the gastrin positive-feed-forward loop was investigated. Gastrin promoter activity was measured in the human gastric carcinoma cell line AGS-CCK2R and in Jurkat cells transfected with various gastrin promoter-luciferase constructs after treatment with gastrin in the presence and absence of zinc-and calcium-chelating agents. The free intracellular zinc ion concentrations were measured in the same cells wi..