Changes in the secretion of insulin-like growth factor binding proteins-2 and-4 associated with the development of tamoxifen resistance and estrogen independence in human breast cancer cell lines

We investigated the secretion of insulin-like growth factor binding protein s (IGFBPs) by estrogen-dependent ZR-75-1 and MCF-7 human breast cancer cell s, and tamoxifen-resistant (ZR-75-9al and LY2) and estrogen-independent (ZR -PR-LT) variants which express altered levels of IGF-I receptor. IGFBP spec ies (35 kDa and 44 kDa) were detectable in conditioned serum-free medium (S FM) by immunoblotting and positively identified as IGFBP-2 and -3, respecti vely. Secretion of IGFBP-2 into SFM by the tamoxifen-resistant and estrogen -independent cell lines was markedly reduced and secretion into SFM of the 24-kDa species, assigned the identity of IGFBP-4, was also reduced in the t amoxifen-resistant lines. There was no clear correlation between patterns o f IGFBP secretion and IGF-I receptor expression. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.