We examined the potential function of Src in human pancreatic carcinoma. Overexpression of kinase-activated SrcY527F resulted in a significant increase of insulin-like growth factor I (IGF-I)-dependent cell proliferation in the cell line PANC-1. Western blotting and competition binding studies demonstrated 2.3 ± 0.2-fold increase in IGF-I receptor expression and 2.8 ± 0.4-fold increase in IGF-I-specific binding sites/cell. SrcY527F transfection alone did not change receptor affinity or basal receptor tyrosine phosphorylation, whereas IGF-I-stimulated receptor phosphorylation was increased by 2.1 ± 0.5-fold. IGF-I mRNA expression and protein secretion did not change to exclude autocrine activation. We conclude that Src stimulates IGF-I-dependent proliferation of PANC-1 cells by increasing the number of IGF-I receptors/cell.
This work was supported by the Deutsche Forschungsgemeinschaft (Lu 441/2-2) and by the Bundesministerium für Bildung, Wissenschaft, Forschung und Technik, together with the Land Baden-Württemberg (01 KS 9609/2 and Landesforschungsschwerpunkt II-7532.22-19/23).