title: Fos is required for EGF stimulation of the gastrin promoter.
abstract: Gastrin gene expression is regulated by developmental cues, pH, and inflammation. These processes are mediated by various extracellular ligands, e.g., growth factors, cytokines, and neuropeptides that also stimulate c-fos gene expression. Therefore, to determine whether Fos is required for stimulation of the gastrin promoter, a c-fos sense expression vector was coexpressed with a gastrin reporter construct in a GH4 rat pituitary cell line. We found that epidermal growth factor (EGF) and tumor necrosis factor-alpha (TNF-alpha) transiently stimulate an increase in Fos protein that precedes stimulation of the gastrin promoter. However, the induction mediated by TNF-alpha was weaker than that mediated by EGF, indicating minimal overlap of the signaling pathways activated by EGF and TNF-alpha. Accordingly, overexpression of c-fos mRNA facilitated primarily EGF rather than TNF-alpha induction of the gastrin promoter. Expression of the c-fos gene in the absence of ligand did not stimulate the gastrin promoter. Thus c-fos gene expression is required but is not sufficient for induction of the gastrin promoter by EGF.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
authors.forename: P
authors.initials: P
authors.lastname: Marks
authors.forename: G
authors.initials: G
authors.lastname: Iyer
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.forename: J L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000818:Animals; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005755:Gastrins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos; D010902:Pituitary Gland / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005755:Gastrins; D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor