Potential role of the epidermal growth factor receptor in human pancreatic cancer

摘要

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-α). 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-α and are capable of binding exogenous TGF-α. They often recycle EGF, but markedly and rapidly degrade TGF-α. However, TGF-α 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-α in this regard. The concomitant overexpression of the EGF receptor and production of TGF-α, the recycling of EGF, and the attenuated ability of TGF-α to down-regulate the EGF receptor may combine to provide a distinct growth advantage to human pancreatic can