BETACELLULIN, A MEMBER OF THE EPIDERMAL GROWTH-FACTOR FAMILY, IS OVEREXPRESSED IN HUMAN PANCREATIC-CANCER

Human pancreatic ductal adenocarcinomas overexpress the epidermal grow th factor (EGF) receptor. Betacellulin is a mitogenic polypeptide that binds and activates this receptor. To determine whether betacellulin has a role in human pancreatic cancer, we studied its expression in cu ltured human pancreatic cancer cell lines and in normal and cancerous pancreatic tissues. Five of 6 pancreatic cancer cell lines expressed t he 3 kb betacellulin mRNA moiety, T3M4, MiaPaCa-2 and COLO-357 cells e xhibiting the highest expression levels. EGF, heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) inc reased betacelullin mRNA levels. Only 2 of 15 normal samples and 1 of 10 cancer samples failed to exhibit the betacellulin transcript. Densi tometric analysis of the autoradiographs revealed a 7.5-fold increase in betacellulin mRNA levels in the cancer tissues by comparison with t he normal tissues. By in situ hybridization, the duct-like cancer cell s exhibited many betacellulin mRNA in situ hybridization grains. These findings indicate that human pancreatic cancer cells express betacell ulin in culture and in vivo, and suggest that this EGF-like ligand may participate in aberrant autocrine and paracrine activation of the EGF receptor in human pancreatic cancer.