Insulin-like growth factor binding protein-3 increases intracellular calcium concentrations in MCF-7 breast carcinoma cells.
Insulin-like growth factor binding protein-3, IGFBP-3, specifically binds to IGFs with high affinity, but it is also capable of modulating the IGF-I signalling pathway or inducing apoptosis independently of its binding to IGFs. The molecular mechanisms underlying the action of IGFBP-3 have not been elucidated. In this study, we have demonstrated that binding of IGFBP-3 to a cell surface receptor in MCF-7 breast carcinoma cells induces a rapid and transient increase in intracellular free calcium. This increase was mediated via a pertussis toxin-sensitive pathway, indicating that the IGFBP-3 receptor may be specifically coupled to a Gi protein. The effect of IGFBP-3 on calcium concentrations was dose-dependent and also occurred when IGFBP-3 was complexed with either IGF-I or heparin, suggesting that the receptor binding site is probably located in the least conserved central domain of IGFBP-3. Neither IGFBP-1, nor IGFBP-5 (structurally the closest to IGFBP-3) altered intracellular calcium concentrations. These results provide evidence that a specific intracellular signal is triggered by IGFBP-3 binding to a cell surface receptor.
Ricort
Jean-Marc
JM
Institut National de la Santé et de la Recherche Médicale, Unité 515, Hôpital Saint-Antoine, 184 rue du Fbg St-Antoine, 75012, Paris, France. ricort@st-antoine.inserm.fr
Lombet
Alain
A
Lassarre
Claudine
C
Binoux
Michel
M
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism* / Q000494:pharmacology; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000378:metabolism / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D011956:Receptors, Cell Surface; D019284:Thapsigargin; D007334:Insulin-Like Growth Factor I; D006493:Heparin; D037342:Pertussis Toxin; D002118:Calcium