Two human pancreatic adenocarcinoma cell lines (PANC 1 and MIA PACA 2) were examined for expression of growth factors that could potentially play a role either in growth regulation of the tumor cells, or in cells that comprise the stromal elements of tumors. Both cell lines expressed transforming growth factor-α (TGFα), basic fibroblast growth factor (bFGF), c-sis (PDGF B chain), TGFβ1, and TGFβ3 mRNA by Northern blot analysis. Only the PANC 1 cells, however, expressed the TGFβ2 transcript. TGFP-like competing activity was found in medium conditioned by either cell line, but TGFα-like [epidermal growth factor (EGF)-competing] activity was not detected in the medium from either cell line by radioreceptor assay. TGFα and EGF caused concentration-dependent stimulation of soft agar colony growth of the MIA PACA 2 cells, while only TGFα caused a significant but less dramatic stimulation of soft agar growth of the PANC 1 cells. Insulin stimulated the anchorage-independent growth of MIA PACA 2 but not PANC 1 cells. Likewise, bFGF also caused a concentration-dependent stimulation of MIA PACA 2 but not PANC 1 growth in soft agar, and PDGF had no effect on the growth of either cell line. TGFβ had no inhibitory or stimulatory effect on soft agar colony growth of either the PANC 1 or the MIA PACA 2 cells, although both cell lines exhibited high affhity, saturable TGFβ binding sites, and TGFβl was capable of autoinduction of TGFβ1 mRNA expression in PANC 1 cells. The ability to continue to respond to positive growth regulatory factors coupled with the loss of responsiveness to negative growth factors may be important in the pathogenicity of these aggressive tumors.