Immunohistochemical localization of betacellulin, a new member of the EGF family, in normal human pancreas and islet tumor cells

Betacellulin (BTC) purified from mouse beta cell tumor (beta TC-3) is a new member of the epidermal growth factor (EGF) family which can bind receptor tyrosine kinase, EGF receptor (erbB1) and erbB4. It has been demonstrated that proBTC mRNA was abundantly expressed in human pancreas tissue, and that ETC converted amylase-secreting rat acinar cell line (AR42J) into insulin-secreting cells, suggesting that ETC might be important for the growth and/or differentiation of islet cells. However, the cell type producing ETC in the pancreas has not been clarified. In this study, we examined the localization of ETC in human pancreas and islet cell tumors. Immunohistochemistry using specific antibodies to human ETC revealed that this protein was produced in alpha cells and duct cells, and probably in beta cells in normal adult pancreas. Furthermore, strong immunoreactivity to ETC was detected in primitive duct cells of the fetal pancreas, and both insulinoma and glucagonoma cells also showed positive immunoreactivity to ETC. EGF receptor (erbB1) and erbB4 were expressed mainly in islet and duct cells, and duct cells, respectively. These results demonstrate the localization of ETC and its receptors, and suggest that ETC may be one of the factors that have physiologically important roles such as growth and differentiation of islet cells in the human pancreas.