Estrogen and antiestrogen modulation of MCF7 human breast cancer cell proliferation is associated with specific alterations in accumulation of insulin-like growth factor-binding proteins in conditioned media.

Abstract

Many neoplastic cell lines secrete insulin-like growth factor binding proteins (IGFBPs). The physiological role of these proteins is incompletely characterized; under various conditions IGFBPs have been observed to either enhance or inhibit the biological activity of insulin-like growth factors. MCF7 human breast cancer cells are known to be mitogenically responsive to insulin-like growth factors and estrogens, to secrete several IGFBPs, including BP-2, BP-4 and BP-5, and to be growth inhibited by antiestrogens. We report here that the pure antiestrogen ICI 182,780 and, to a lesser extent, the commonly used drug tamoxifen significantly increase levels of a M(r) 43,000-46,000 IGFBP (BP-3) and significantly reduce levels of a M(r) 24,000 IGFBP (BP-4) in the conditioned medium of MCF7 cells. Effects of estradiol and antiestrogens on M(r) 30,000 and M(r) 36,000 IGFBPs are also described. The effects of ICI 182,780 on IGFBPs in the conditioned medium of MCF7 cells may contribute to the remarkable ability of this compound to attenuate insulin-like growth factor I stimulated MCF7 cell proliferation.