Essential roles of IGFBP-3 and IGFBP-rP1 in breast cancer.
Insulin and insulin-like growth factors (IGFs) have critical functions in growth regulatory signalling pathways. They are part of a tightly controlled network of ligands, receptors, binding proteins and their proteases. However, the system becomes uncontrolled in neoplasia. The insulin-like growth factor binding protein 3 (IGFBP-3) and the insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) have unique properties among the sixteen known members of the IGFBP superfamily. IGFBP-3 has very high affinity for IGFs (k(d) approximately 10(-10) M), it transports >75% of serum IGF-I and -II, whereas it's affinity for insulin is very low. On the other hand, IGFBP-rP1 binds insulin with very high affinity (500-fold higher compared to other IGFBPs), but has low affinity for IGF-I and -II proteins (k(d) = 3 x 10(-8) M). In this review, we have examined the roles of IGFBP-3 and IGFBP-rP1 in breast cancer, and discuss the potential impact of these two proteins in mammary carcinoma risk assessment and the development of treatments for breast cancer.
Laboratory of Molecular Pathology, Department of Anatomic Pathology and Division of Molecular and Cellular Biology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ont., Canada. angelikaburger@aol.com
Angelika M
AM
Burger
Brian
B
Leyland-Jones
Kris
K
Banerjee
Demetri D
DD
Spyropoulos
Arun K
AK
Seth
D001943:Breast Neoplasms / Q000209:etiology* / Q000628:therapy; D002450:Cell Communication / Q000502:physiology; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use
D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D011994:Recombinant Proteins; C102529:insulin-like growth factor binding protein-related protein 1