AJP - Cell Physiology, Vol 269, Issue 6 C1474-C1481, Copyright © 1995 by American Physiological Society

ARTICLES

Gastrin stimulates expression of protooncogene c-myc through a process involving polyamines in IEC-6 cells

J. Y. Wang, H. Wang and L. R. Johnson
Department of Physiology and Biophysics, University of Tennessee College of Medicine, Memphis 38163, USA.

The current study tested the hypothesis that the protooncogene 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 protooncogene, and 2) depletion of intracellular polyamines by DFMO significantly prevented the increased expression of c-myc by gastrin.

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