AJP - Gastrointestinal and Liver Physiology, Vol 273, Issue 2 389-G398, Copyright © 1997 by American Physiological Society

ARTICLES

Increased expression of EGFR in gastric mucosa of aged rats

J. Tureaud, F. H. Sarkar, S. E. Fligiel, S. Kulkarni, R. Jaszewski, K. Reddy, Y. Yu and A. P. Majumdar
Veterans Affairs Medical Center, Detroit, Michigan, USA.

Although in Fischer-344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about the intracellular events that regulate this process. The present investigation examines the age-related changes in gastric mucosal tyrosine kinase activity and expression of epidermal growth factor receptor(EGFR) and its structural and functional analog p185c-erbB-2, the protein product of c-erbB-2/c-neu protooncogene. We observed a significantly higher intrinsic tyrosine kinase activity and tyrosine phosphorylation of EGFR and p185c-erbB-2 in the gastric mucosa of 24-mo-old (aged) rats than in that of their 4- or 12-mo-old counterparts. This was associated with increased levels of EGFR protein and steady-state mRNA levels of EGFR and p185c-erbB-2. In addition, we also observed threefold higher steady-state mRNA levels of transforming growth factor-alpha (TGF-alpha; one of the primary ligands of EGFR) in the gastric mucosa of aged rats than in that of 4-mo-old (young) animals. This was accompanied by a fivefold increase in the relative concentration of the 18-kDa precursor form of TGF-alpha in gastric mucosal membranes but not in the cytosol. In conclusion, our data demonstrate that aging is associated with increased tyrosine kinase activity of EGFR and p185c-erbB-2 in the gastric mucosa. Moreover, the observation that aging results in increased accumulation of TGF-alpha in gastric mucosal membranes raises the possibility that the membrane-bound TGF-alpha could partly be responsible for the constitutively active EGFR-induced signaling pathway in the gastric mucosa of aged rats and, in turn, for stimulation of mucosal proliferative activity.

This article has been cited by other articles:

				A. P. N. Majumdar, J. Du, Y. Yu, H. Xu, E. Levi, B. B. Patel, and A. K. Rishi Cell cycle and apoptosis regulatory protein-1: a novel regulator of apoptosis in the colonic mucosa during aging Am J Physiol Gastrointest Liver Physiol, December 1, 2007; 293(6): G1215 - G1222. [Abstract] [Full Text] [PDF]

				A. P. N. Majumdar and J. Du Phosphatidylinositol 3-kinase/Akt signaling stimulates colonic mucosal cell survival during aging Am J Physiol Gastrointest Liver Physiol, January 1, 2006; 290(1): G49 - G55. [Abstract] [Full Text] [PDF]

				Z.-Q. Xiao, J. Li, and A. P. N. Majumdar Regulation of TGF-{alpha}-induced activation of AP-1 in the aging gastric mucosa Am J Physiol Gastrointest Liver Physiol, July 7, 2003; 285(2): G396 - G403. [Abstract] [Full Text] [PDF]

				L. Moragoda, R. Jaszewski, P. Kulkarni, and A. P. N. Majumdar Age-associated loss of heterozygosity of tumor suppressor genes in the gastric mucosa of humans Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G932 - G936. [Abstract] [Full Text] [PDF]

				Z.-Q. Xiao and A. P. N. Majumdar Increased in vitro activation of EGFR by membrane-bound TGF-{alpha} from gastric and colonic mucosa of aged rats Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G111 - G116. [Abstract] [Full Text] [PDF]

				Y. Yu, A. K. Rishi, J. R. Turner, D. Liu, E. D. Black, J. A. Moshier, and A. P. N. Majumdar Cloning of a novel EGFR-related peptide: a putative negative regulator of EGFR Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1083 - C1089. [Abstract] [Full Text] [PDF]

				Z.-Q. Xiao and A. P. N. Majumdar Induction of transcriptional activity of AP-1 and NF-kappa B in the gastric mucosa during aging Am J Physiol Gastrointest Liver Physiol, June 1, 2000; 278(6): G855 - G865. [Abstract] [Full Text] [PDF]

				J. R. Turner, L. Liu, S. E. G. Fligiel, R. Jaszewski, and A. P. N. Majumdar Aging alters gastric mucosal responses to epidermal growth factor and transforming growth factor-alpha Am J Physiol Gastrointest Liver Physiol, May 1, 2000; 278(5): G805 - G810. [Abstract] [Full Text] [PDF]

				M. J. Rutten, K. D. Bacon, K. L. Marlink, M. Stoney, C. L. Meichsner, F. P. Lee, S. A. Hobson, K. D. Rodland, B. C. Sheppard, D. D. Trunkey, et al. Identification of a functional Ca2+-sensing receptor in normal human gastric mucous epithelial cells Am J Physiol Gastrointest Liver Physiol, September 1, 1999; 277(3): G662 - G670. [Abstract] [Full Text] [PDF]

				L. Liu, J. R. Turner, Y. Yu, A. J. Khan, R. Jaszewski, S. E. G. Fligiel, and A. P. N. Majumdar Differential expression of EGFR during early reparative phase of the gastric mucosa between young and aged rats Am J Physiol Gastrointest Liver Physiol, November 1, 1998; 275(5): G943 - G950. [Abstract] [Full Text] [PDF]

				A. P. N. Majumdar and J. R. Goldenring Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity Am J Physiol Gastrointest Liver Physiol, May 1, 1998; 274(5): G863 - G870. [Abstract] [Full Text] [PDF]