The mRNA expression of IGF-1 and IGF-1R in human breast cancer: Association with clinico-pathological parameters

W Al Sarakbi, YM Chong, SLJ Williams, AK Sharma, K Mokbel
Breast Unit St.George’s Hospital and Medical School Tooting, London SW17 0QT, United Kingdom
DOI: 10.1186/1477-3163-5-16


The insulin-like growth factor-I (IGF-I) receptor is a member of a large family of transmembrane signal transducing molecules. The IGF system is composed of IGF ligands, receptors, and binding proteins. These system components form a highly regulated network of interactions both among themselves and between other biologic signalling pathways [1,2].

There are two characterised ligands, IGF-I and IGF-II whose activities are mainly mediated by type I and II receptors [1,3]. IGF–1R is necessary for the normal progression through the cell cycle and for normal growth and development [4,5].

The principal pathways for transduction of the IGF signal are mitogen-activated protein kinase and phosphatidylinositol 3′-kinase [6,7]. After ligand-dependent receptor autophosphorylation, the IGF-IR phosphorylates a series of adaptor proteins, including insulin receptor substrate–1, to activate intracellular signalling cascades [7]. The protein kinase pathway is responsible for the mitogenic signal observed after IGF stimulation but may also be accountable for cell survival in cells over expressing the IGF–1R [8]. The IGF system has been implicated in promoting mitogenic, metastatic, and antiapoptotic phenotypes in breast cancer. As a consequence of the ability of IGF to promote tumorigenesis, pharmacologic interventions targeting the IGF system are being devised [9-11]. It is believed that IGF–1 can affect breast cells through endocrine, autocrine, and paracrine mechanisms [12-14]. Read More…