Gastrin is the major gastrointestinal hormone known to regulate both acid secretion and gastrointestinal cell growth.
The specific aims of this application are to a) examine the inducible expression of the human gastrin gene in human gastric cell lines and b) to define the signaling pathways relevant for inducible control of the gastrin promoter via gERE. Inducible and tissue specific regulation of the gastrin promoter by Sp1 and ZBP-89 will be tested in human stomach cell lines. In addition, the regulation of these specific transcription factors by phosphorylation will be studied using in vitro kinase assays and in vivo by immunoprecipitating the phosphorylated factors for peptide mapping. The identification of a transcriptional repressor and studying how it inhibits gastrin promoter activation will permit the design of additional therapies that block gastrin synthesis and perhaps the pathologic consequences of hypergastrinemia.
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