Src stimulates insulin-like growth factor I (IGF-I)-dependent cell proliferation by increasing IGF-I receptor number in human pancreatic carcinoma cells.
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.
Department of Internal Medicine, University of Ulm, Germany.
B B
BB
Flossmann-Kast
P M
PM
Jehle
A
A
Hoeflich
G
G
Adler
M P
MP
Lutz
D002455:Cell Division; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D009363:Neoplasm Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D016392:Proto-Oncogene Proteins pp60(c-src)