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1 Division of Digestive Diseases and Nutrition, UMass Memorial Medical Center, Worcester, MA, USA
2 Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA
3 GastrointestinaI Sciences, Manchester University, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: timothy.wang{at}umassmed.edu.
Gastrin is a known growth/differentiation factor for the gastric mucosa.Its' effects are likely mediated by the induction of HB-EGF, a member of the EGF family of growth factors that is expressed by gastric parietal cells. In this study, we investigated the regulation of the HB-EGF promoter by gastrin in a human gastric cancer cell line. Serial human HB-EGF promoter-luciferase reporter deletion constructs and heterologous promoter constructs were transfected into AGS-E cells and stimulated with gastrin (10- 7M) with or without various signal transduction inhibitors. Electromobility shift assays were also performed. Gastrin stimulation resulted in a 5-fold increase in HB-EGFluciferase activity. The cis-acting element mediating gastrin-responsiveness was mapped to the -69 to -58 region of the HB-EGF promoter. Gastrin stimulation was PKC-dependent, and at least partially mediated by activation of the EGF receptor.
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