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.
Burger
Angelika M
AM
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
Leyland-Jones
Brian
B
Banerjee
Kris
K
Spyropoulos
Demetri D
DD
Seth
Arun K
AK
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