Systemic treatment with epidermal growth factor in pigs induces ductal proliferations in the pancreas

Abstract

Background and Aims: Epidermal growth factor (EGF), transforming growth factor α (TGF-α), and the EGF receptor are often overexpressed in chronic pancreatitis and in malignant pancreatic growth. Transgenic mice overexpressing TGF-α develop tissue changes in the pancreas resembling changes found in chronic pancreatitis. The effects of systemic treatment with EGF on the porcine pancreas were investigated in this study. Methods: Mature Goettingen minipigs were treated with solvent (n =5), EGF (30 μg · kg-1 · day-1; n = 6) for 4 weeks, or EGF(30 μg · kg-1 · day-1; n = 5) for 5 weeks followed by 3 weeks of recovery. Pancreata were studied by routine histological examination and electron microscopy and were immunostained for proliferating cell nuclear antigen (PCNA). Results: In the EGF-treated animals, mainly larger interlobular ducts of the pancreas appeared to be considerably hyperplastic, with an increased number of nuclei that stained for PCNA. The epithelia of these ducts were increased in height, with accumulations of glycoconjugates in the columnar cells and in an increased number of goblet cells. Conclusions: A new approach to experimentally induced hyperplastic changes of the excretory ducts of the pancreas is presented. Because ductal changes with glycoconjugate accumulations are common features of chronic pancreatitis and pancreatic cancer, the findings may be relevant to the pathogeneses of these conditions.