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Reduced Expression of Epidermal Growth Factor Receptors in Rat Liver During Aging

Departments of ¹ Medicine, ² Surgery, and ³ Dental Diagnostic Science, University of Texas Health Science Center at San Antonio.
⁴ Geriatric Research Education and Clinical Center, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio.

Address correspondence to Amrita Kamat, PhD, Geriatric Research Education and Clinical Center (182), Audie L. Murphy Division, South Texas Veterans Health Care System, 7400 Merton Minter Blvd., San Antonio, TX 78229. E-mail: kamat{at}uthscsa.edu

Proliferative responsiveness of hepatocytes to epidermal growth factor (EGF) declines during aging. The role of EGF receptors in mediating age-dependent changes of EGF-induced mitogenic signaling in liver remains incompletely understood. We assessed EGF receptor expression levels in whole liver specimens as well as in freshly isolated and cultured hepatocytes from young adult and senescent Fischer 344 male rats. Hepatic EGF receptor messenger RNA and protein levels, and the number of high- and low-affinity receptor binding sites, decreased with aging. Ligand-induced EGF receptor activation, determined by receptor dimerization and tyrosine phosphorylation, was reduced in old animals in parallel with the age-related decline in receptor expression. Stimulation of the extracellular signal-regulated kinase pathway by EGF was also attenuated in hepatocytes from old animals. Our results implicate decreased expression of EGF receptors as a key determinant of reduced mitogenic signaling responsive to EGF stimulation of liver during aging.

Key Words: Extracellular signal-regulated kinase • Hepatocytes • Receptor dimerization • Receptor tyrosine kinase