Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism

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...

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Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2004-06, Vol.286 (6), p.G992-G999
Main Authors: Sinclair, Natalie F, Ai, Wandong, Raychowdhury, Raktima, Bi, Meixia, Wang, Timothy C, Koh, Theodore J, McLaughlin, John T
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cell Nucleus - metabolism
Epidermal Growth Factor - genetics
Epidermal Growth Factor - metabolism
Gastrins - genetics
Gastrins - pharmacology
Gastrins - physiology
Heparin-binding EGF-like Growth Factor
Humans
Intercellular Signaling Peptides and Proteins
Mice
Promoter Regions, Genetic - drug effects
Promoter Regions, Genetic - genetics
Promoter Regions, Genetic - physiology
Protein Kinase C - physiology
Receptor, Epidermal Growth Factor - physiology
Response Elements - genetics
Response Elements - physiology
Signal Transduction
Sp1 Transcription Factor - physiology
Stereoisomerism
Transcription Factors - metabolism
Ultraviolet Rays
Zinc - metabolism
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Summary: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.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.00206.2002