AJP - Gastrointestinal and Liver Physiology, Vol 266, Issue 5 878-G886, Copyright © 1994 by American Physiological Society

ARTICLES

Expression of protooncogenes c-fos and c-myc in healing of gastric mucosal stress ulcers

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

The current study determines the hypothesis that expression of protooncogenes c-fos and c-myc is involved in the mechanism of polyamine-stimulated healing in gastric mucosal stress ulcers. Rats were fasted 22 h, placed in restraint cages, and immersed in water to the xiphoid process for 2-6 h. Animals were killed either immediately after stress or at 2-h intervals up to 24 h after 6 h of stress. Stress caused both visible lesions and induction of ornithine decarboxylase (ODC) activity in the oxyntic gland mucosa after 2 h. Increased ODC activity was paralleled by increases in the mucosal polyamines putrescine, spermidine, and spermine. Exposure to stress led to appearance of c-fos mRNA and oncoprotein in the gastric oxyntic gland mucosa at 2 h and its disappearance by 4 h. Baseline expression of c-myc was enhanced significantly after 6 h of stress and remained elevated for 4 h. This change in the expression of c-fos and c-myc mRNA and oncoprotein preceded an increased rate of [3H]thymidine incorporation into mucosal DNA. Administration of alpha-difluoromethylornithine (DFMO, 500 mg/kg ip) totally prevented the marked increases in ODC activity and polyamine levels. DFMO also completely inhibited the expression of c-fos and significantly decreased c-myc mRNA and oncoprotein in the gastric mucosa of stressed rats. The healing process, which was significant by 12 h, was markedly inhibited by DFMO. These results show that 1) mucosa exposed to stress exhibits increased expression of c-fos and c-myc following increased polyamine synthesis and 2) inhibition of polyamine biosynthesis by DFMO decreases both protooncogene expression and mucosal healing.

This article has been cited by other articles:

				T. Zou, J. N. Rao, L. Liu, B. S. Marasa, K. M. Keledjian, A.-H. Zhang, L. Xiao, B. L. Bass, and J.-Y. Wang Polyamine depletion induces nucleophosmin modulating stability and transcriptional activity of p53 in intestinal epithelial cells Am J Physiol Cell Physiol, September 1, 2005; 289(3): C686 - C696. [Abstract] [Full Text] [PDF]

				L. Liu, L. Li, J. N. Rao, T. Zou, H. M. Zhang, D. Boneva, M. S. Bernard, and J.-Y. Wang Polyamine-modulated expression of c-myc plays a critical role in stimulation of normal intestinal epithelial cell proliferation Am J Physiol Cell Physiol, January 1, 2005; 288(1): C89 - C99. [Abstract] [Full Text] [PDF]

				L. Liu, R. Santora, J. N. Rao, X. Guo, T. Zou, H. M. Zhang, D. J. Turner, and J.-Y. Wang Activation of TGF-{beta}-Smad signaling pathway following polyamine depletion in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, November 1, 2003; 285(5): G1056 - G1067. [Abstract] [Full Text] [PDF]

				W-M WONG, R J PLAYFORD, and N A WRIGHT Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy? Gut, February 1, 2000; 46(2): 286 - 292. [Full Text] [PDF]

				L. Li, J. Li, J. N. Rao, M. Li, B. L. Bass, and J.-Y. Wang Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis Am J Physiol Cell Physiol, April 1, 1999; 276(4): C946 - C954. [Abstract] [Full Text] [PDF]

				L. R. Johnson and S. A. McCormack Healing of Gastrointestinal Mucosa: Involvement of Polyamines Physiology, February 1, 1999; 14(1): 12 - 17. [Abstract] [Full Text] [PDF]

				A. R. Patel and J.-Y. Wang Polyamine depletion is associated with an increase in JunD/AP-1 activity in small intestinal crypt cells Am J Physiol Gastrointest Liver Physiol, February 1, 1999; 276(2): G441 - G450. [Abstract] [Full Text] [PDF]

				A. R. Patel, J. Li, B. L. Bass, and J.-Y. Wang Expression of the transforming growth factor-beta gene during growth inhibition following polyamine depletion Am J Physiol Cell Physiol, August 1, 1998; 275(2): C590 - C598. [Abstract] [Full Text] [PDF]