Gastrin stimulates the expression of proto-oncogene c-myc through a
process involving polyamines in iec-6 cells.
Wang, Jian-Ying, Hanlin Wang, and Leonard R. Johnson.
Departments of Physiology and Biophysics and Pathology, University
of Tennessee College of Medicine, Memphis, TN 38163
APStracts 2:0305C, 1995.
The current study tested the hypothesis that the proto-oncogene c-myc
is involved in the mechanism by which gastrin modulates mucosal cell
proliferation. Studies were conducted in the IEC-6 cell line, derived
from rat small intestinal crypt cells. Administration of gastrin
resulted in the rapid appearance of c-myc mRNA in IEC-6 cells. The
increased expression of c-myc began 1 h and peaked 4 h after exposure
to gastrin. Maximum increase in c-myc mRNA levels was 7.5-fold the
normal value. When cellular protein synthesis was inhibited by
addition of cycloheximide, gastrin superinduced c-myc mRNA levels.
Gastrin also significantly increased the mRNA levels for ornithine
decarboxylase (ODC), the rate limiting enzyme for polyamine
biosynthesis, enzyme activity and intracellular polyamines in IEC-6
cells. Treatment with [alpha]-difluoromethylornithine (DFMO), a
specific inhibitor of ODC, not only completely depleted intracellular
polyamines but also significantly prevented the increased expression
of c-myc in cells exposed to gastrin. These results show that 1)
gastrin stimulates both polyamine biosynthesis and the expression of
the c-myc proto-onocgene, and 2) depletion of intracellular
polyamines by DFMO significantly prevented the increased expression
of c-myc by gastrin.
Received 13 February 1995; accepted in final form 13 June 1995.
APS Manuscript Number C77-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.