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) - 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. (c) 2005 Elsevier Ltd. All rights reserved.