Background: The insulin-like growth factors (IGFs) play an important role in normal growth and development. Evidence suggests they may also regulate the growth of several cancer cell types. This regulation is mediated by interactions between the receptors and ligands. There is now ample evidence to sugest that these interactions are also influenced by extracellular IGFbinding proteins (IGFBPs). Six different IGFBPs have been cloned. Some species may act to inhibit the mitogenic effects of the IGFs. Since breast cancer cells are responsive to the IGFs, it is possilble that regulated expression of the IGFBPs affects tumor growth. Furthermore, inhibitory binding proteins could be used as neutralizers of IGF action. Purpose: We conducted this study to fully characterize the expression and hormonal regulation of IGF-binding protein expression in human MCF-7 breast cancer cells and to test the ability of purifies IGFBP-1 to inhibit IGF-I action. Methods: We used ribonuclease protection assays and Western ligang blotting to examine IGFBP expression in MCF-7 cells. The effect of IGF-1, IGFBP-1, and 17β estradiol on serum- free cell growth was also studied. Results: MCF-7 cells expressed IGFBP-2, IGFBP-4, and IGFBP-5 RNa and protein. These cells are dependent on estrogen for growth. In short- term culture.IGF-1can substitute for estrogen. Concomitant addition of IGF-I and estrogen achieved by either factor alone estrogen also increased IGFBP production, making it unlikely that the IGFBPs induced by estrogen in MCF-7 cells function as major inhibitors of IGF action. In contrast, exogenous addtion of IGFBP-1 could block IGF-I-induced mitogenesis; this effect was reversible by excessIGF-I.

Conclusions: The stidies suggest that cancer cell growth may be regulated by endogenous IGFBP expression Furthermore, the exogenous addtion of the IGFBP-1 blocked IGF-1 action and potentially could be used as a pharmacolgic inhibitor of IGF action. [J Natl Cancer Inst 84: 1336–1341, 1992]