Cytokine-Mediated Regulation of Growth Factor Receptors (EGF-R and erb-B2) in Pancreatic Tumors

Abstract

The growth of normal and neoplastic cells is generally believed to depend on a concerted regulation of growth factor signals which are mediated via specific membrane receptors to the nuclear target structures. The family of growth factor receptors is divided into subgroups according to their functional and structural domains (review: [13]). Three very closely related members of the tyrosine kinase subgroup are the epidermal growth factor receptor,EGF-R/erb-B1 with transforming growth factor alpha (TGF-α) and EGF as ligands [12], the related erb-B2/c-neu receptor with one candidate ligand [10] and the recently descirbed erb-B3 receptor with no known ligand [8]. Despite the important progress in our knowledge, which has been based on structural analyses after cloning the respective genes, the regulation and the interdependent activities of these signal-transducing cellular compounds remain to be fully characterized. Within the concert of signals triggering cellular growth and differentiation, lymphokines and interleukins — produced predominantly, but not exclusively, by hematopoietic cells — are thought to play a major role. The network of cytokines (review: [1]) comprises factors like tumor necrosis factor alpha (TNF-α) and lymphotoxin (LT or TNF-β) which were originally thought to play a key role in the body’s defense against transformed cells, but whose pluripotent activities are now becoming more and more evident [3].