The insulin-like growth factors (IGFs) have been implicated in the growth regulation of human breast cancer. Since the IGFs are associated with specific binding proteins (IGFBPs) which may modulate receptor/ligand interactions, production of IGFBPs by breast cancer cells could alter their IGF-dependent growth. This study examined the expression of IGFBPs 4, 5, and 6 in eight breast cancer cell lines (BCCLs) using ribonuclease (RNase) protection assays. IGFBP-4 mRNA was detected in all BCCLs studied. IGFBP-5 expression was higher in estrogen receptor (ER) positive cells, while IGFBP-6 mRNA was detected in only two ER negative BCCLs. We also found that E2 treatment enhanced the expression of IGFBPs 2, 4, and 5 in T47-D cells. We next studied IGFBP mRNA expression in 40 primary breast tumors. All tumors expressed mRNA for IGFBPs 2-6 but none expressed IGFBP-1 message. IGFBP-3 expression was higher in ER negative tumors, while that of IGFBP-4 and -5 was higher in ER positive specimens. These differences were statistically significant (P < .05). Ligand blot analysis of tumor extracts confirmed the presence of IGFBPs in breast cancer tissues. Thus, differential IGFBP expression in ER positive and negative tumors suggests an important role for this protein in breast cancer biology.

The insulin-like growth factors (IGFs) have important roles in normal cellular growth and development. The IGFs have also been implicated in regulation of tumor cell growth. Two ligands, IGF-I and IGF-II, have been identified that are expressed in both fetal and adult tissues. They interact with at least two specific cell surface receptors. The type I IGF receptor is homologous to the insulin receptor in structure and has tyrosine kinase activity. The type II receptor is identical to the mannose-6-phosphate receptor known to be important in the trafficking of lysosomal enzymes; its role in IGF signal transduction is not clear. Furthermore, a hybrid receptor composed of subunits from the insulin receptor and the type I IGF receptor have been identified. In addition to these receptors, six different IGF binding proteins have been identified, which modulate the activity of the IGFs in various ways. Thus, there is great potential for complex interactions between the family members that could ultimately regulate normal and neoplastic cell growth.

No abstract