IGFBPs and breast cancer

The IGFBP family comprises 6 proteins with high affinity for the IGFs, there are also several much lower affinity IGFBP-related proteins. Their production in the breast is controlled by hormones, other local regulators and in tumours relates to the estrogen receptor status. Their functional activity can also be affected by various post-translational modifications, including proteolysis, phosphorylation and glycosylation. The IGFs are generally present at levels far in excess of that required for maximal receptor stimulation, and the IGFBPs are critical regulators of their cellular actions. IGFBPs can affect cell function in an IGF-dependent or independent manner. IGF bioactivity locally in the breast is influenced not only by local tissue expression and regulation of IGFs, IGFBPs and IGFBP proteases, but also by these factors delivered from the circulation. Changes in the balance of the components of the IGF system may lead to a disruption of tissue homeostasis.