Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism
University of Massachusetts Memorial Medical Center, Division of Digestive Diseases and Nutrition
Animals; Cell Line, Tumor; Cell Nucleus; Epidermal Growth Factor; Gastrins; Humans; Intercellular Signaling Peptides and Proteins; Mice; Promoter Regions (Genetics); Protein Kinase C; Receptor, Epidermal Growth Factor; Response Elements; Signal Transduction; Sp1 Transcription Factor; Stereoisomerism; Transcription Factors; Ultraviolet Rays; Zinc
Life Sciences | Medicine and Health Sciences
Gastrin is a known growth/differentiation factor for the gastric mucosa. Its effects are likely mediated by the induction of heparin-binding epidermal-like growth factor (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(-7) M) with or without various signal transduction inhibitors. EMSA were also performed. Gastrin stimulation resulted in a fivefold increase in HB-EGF-luciferase 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.
DOI of Published Version
Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G992-9. Link to article on publisher's site
American journal of physiology. Gastrointestinal and liver physiology
Sinclair, Natalie F.; Ai, Wandong; Raychowdhury, Raktima; Bi, Meixia; Wang, Timothy C.; Koh, Theodore J.; and McLaughlin, John T., "Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism" (2004). Open Access Articles. 119.