Fos is required for egf stimulation of the gastrin promoter.
Marks, Patricia, Gaitry Iyer, Yingqi Cui, Juanita L. Merchant.
Departments of Internal Medicine and Physiology, University of
Michigan and the Howard Hughes Medical Institute, Ann Arbor, Michigan
48109
APStracts 3:0129G, 1996.
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 cfos gene expression. Therefore to determine whether Fos is
required for stimulation of the gastrin promoter, a cfos sense
expression vector was coexpressed with a gastrin reporter construct
in a GH4 rat pituitary cell line. We found that EGF and 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 cfos mRNA facilitated primarily EGF
rather than TNF[alpha] induction of the gastrin promoter. Expression
of the cfos gene in the absence of ligand did not stimulate the
gastrin promoter. Thus, cfos gene expression is required but is not
sufficient for induction of the gastrin promoter by EGF.
Received 2 January 1996; accepted in final form 10 June 1996.
APS Manuscript Number G4-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 July 96