CHRONIC-PANCREATITIS IS ASSOCIATED WITH INCREASED CONCENTRATIONS OF EPIDERMAL GROWTH-FACTOR RECEPTOR, TRANSFORMING GROWTH-FACTOR-ALPHA, ANDPHOSPHOLIPASE C-GAMMA

The epidermal growth factor (EGF) receptor is a transmembrane protein that binds EGF and transforming growth factor alpha (TGF alpha), and t hat stimulates phospholipase C gamma 1 (PLC gamma 1) activity. In this study the role of the EGF receptor in chronic pancreatitis was studie d. By immunohistochemistry the EGF receptor, TGF alpha, and PLC gamma 1 were found to be expressed at high concentrations in pancreatic duct al and acinar cells from chronic pancreatitis patients. Northern blot analysis showed that, by comparison with normal controls, 19 of 27 chr onic pancreatitis tissues exhibited a 5.7-fold increase in EGF recepto r mRNA concentrations, and 20 of 27 chronic pancreatitis tissues exhib ited a sixfold increase in TGF alpha mRNA concentrations. In situ hybr idisation confirmed that overexpression occurred in ductal and acinar cells, and showed that both mRNA moieties colocalised with their respe ctive proteins. These findings suggest that TGF alpha may act through autocrine and paracrine mechanisms to excessively activate the overexp ressed EGF receptor in the two major cell types of the exocrine pancre as, thereby contributing to the pathobiology of this disorder.