Insulin-like growth factor binding protein-3 stimulates phosphatidylinositol 3-kinase in MCF-7 breast carcinoma cells.
Insulin-like growth factor binding protein-3 (IGFBP-3) is the most abundant IGFBP in serum and other biological fluids. Apart from its capacity for specific and high-affinity binding to IGFs, it also has so-called "IGF-independent" activities that modulate cell proliferation and survival/apoptosis. However, the molecular elements of the IGFBP-3 signalling pathway remain obscure. In this study, we investigated the possible implication of phosphatidylinositol 3-kinase (PI 3-kinase) activity in MCF-7 breast carcinoma cells. In cells incubated with IGFBP-3, both total and insulin receptor substrate-1 (IRS-1)-associated PI 3-kinase activities were rapidly stimulated, with maximal effects after 3 and 10min of incubation, respectively. IGFBP-3-induced PI 3-kinase activity was unaffected by the state of IRS-1 tyrosine phosphorylation. Since IGFBP-3 failed to stimulate PI 3-kinase activity in MDA-MB 231 breast carcinoma cells, its effects in MCF-7 cells could be considered as cell-type-specific. Pertussis toxin abolished IGFBP-3-stimulation of PI 3-kinase activity, suggesting that this IGFBP-3 signalling pathway depends upon a pertussis toxin-sensitive G protein. Our results provide further evidence that IGFBP-3 directly triggers a specific intracellular signal in MCF-7 cells.
Ricort
Jean-Marc
JM
Institut National de la Santé et de la Recherche Médicale, Unité 515, Croissance, Différenciation et Processus Tumoraux, Hôpital Saint-Antoine, Paris, France
Binoux
Michel
M
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D029721:Drosophila Proteins / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D037342:Pertussis Toxin / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction
D029721:Drosophila Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D008565:Membrane Proteins; C103615:ifc protein, Drosophila; D037342:Pertussis Toxin; D019869:Phosphatidylinositol 3-Kinases