KERATINOCYTE GROWTH-FACTOR INDUCES PANCREATIC DUCTAL EPITHELIAL PROLIFERATION

Keratinocyte growth factor (KGF) causes a proliferation of pancreatic ductal epithelial cells in adult mts after daily systemic administrati on for 1 to 2 weeks. Even before the proliferation of intralobular duc ts is histologically evident, KGF also induces proliferating cell nucl ear antigen expression within the ductal epithelium of intercalated, i ntralobular, and interlobular ducts. KGF also causes incorporation of 5-bromodeoxyuridine in ductal epithelial cells. Epithelial cell prolif eration is histologically most prominent at the level of the intralobu lar ducts adjacent to and within the islets of Langerhans. Pancreatic ductal proliferation is not histologically apparent in mts sacrificed 7 to 10 days after the cessation of KGF administration. The pancreatic hormones insulin, glucagon, somatostatin, and pancreatic polypeptide are normally distributed within islets that demonstrate intrainsular d uctal proliferation. The proliferating ductal epithelium does not show endocrine differentiation as evidenced by the lack of immunoreactivit y for pancreatic hormones. KGF is a potent in vivo mitogen for pancrea tic ductal epithelial cells.