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Insulin‐like growth factor binding protein‐3 increases intracellular calcium concentrations in MCF‐7 breast carcinoma cells
Author(s) -
Ricort Jean-Marc,
Lombet Alain,
Lassarre Claudine,
Binoux Michel
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03250-7
Subject(s) - intracellular , calcium in biology , mcf 7 , pertussis toxin , receptor , growth factor , calcium , insulin like growth factor binding protein , biology , microbiology and biotechnology , endocrinology , chemistry , medicine , insulin like growth factor , biochemistry , cancer cell , g protein , cancer , genetics , human breast
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.