Src stimulates insulin-like growth factor I (IGF-I) -dependent cell proliferation by increasing IGF-I receptor number in human pancreatic carcinoma cells
Flossmann-Kast, B.B.; Jehle, P.M.; Hoeflich, A.; Adler, G.; Lutz, M.P.
Cancer Research 58(16): 3551-3554
1998
ISSN/ISBN: 0008-5472 PMID: 9721859 Document Number: 493004
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.