Potential role of the epidermal growth factor receptor in human pancreatic cancer.
The epidermal growth factor (EGF) receptor is a transmembrane protein that has tyrosine kinase activity. It is activated by both EGF and transforming growth factor-alpha (TGF-alpha). Human pancreatic cancer cells overexpress the EGF receptor and exhibit a parallel increase in EGF receptor mRNA without a detectable increase in the number of gene copies coding for the receptor. These cells also produce TGF-alpha and are capable of binding exogenous TGF-alpha. They often recycle EGF, but markedly and rapidly degrade TGF-alpha. However, TGF-alpha is 10-100-fold more potent than EGF in enhancing their anchorage-independent growth. Both growth factors induce EGF receptor down-regulation, but EGF is more efficient than TGF-alpha in this regard. The concomitant overexpression of the EGF receptor and production of TGF-alpha, the recycling of EGF, and the attenuated ability of TGF-alpha to down-regulate the EGF receptor may combine to provide a distinct growth advantage to human pancreatic cancer cells.
Korc
M
M
Department of Medicine, University of California, Irvine 92717.
D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors