Limited information is available concerning the involvement of growth factor receptors and their ligands in the pathogenesis of human pancreatic cancer. We analyzed 12 human pancreatic cancer cell lines by Northern blot analysis for the expression of 9 receptor tyrosine kinase (RTKs) and 6 growth factors. The effect of a monoclonal antibody (MAb) against transforming growth factor-alpha (TGF-alpha) on in vitro pancreatic cancer cell growth was also assessed, mRNA for EGF-R, c-erbB-2 and c-erbB-3 was expressed in 12 (100%), 12 (100%), and 7 (58%), respectively, of the cell lines examined. In addition, 8 (67%) cell lines expressed the c-met/receptor for hepatocyte growth factor. As for ligands, TGF-alpha mRNA was detected in 10 (83%) cell lines; MAb against TGF-alpha inhibited growth of the 2 cell lines examined. Furthermore, mRNA for amphiregulin (AR) was expressed in 10 (83%) cell lines. Coexpression of TGF-alpha, AR, and EGF-R was observed in 9 (75%) cell lines. These results support the concept that several specified types of RTKs and their ligands are closely involved in regulation of the growth of human pancreatic cancer cells.