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 proteins (IGFBPs) by estrogen-dependent ZR-75-1 and MCF-7 human breast cancer cells, and tamoxifen-resistant (ZR-75-9a1 and LY2) and estrogen-independent (ZR-PR-LT) variants which express altered levels of IGF-I receptor. IGFBP species (35 kDa and 44 kDa) were detectable in conditioned serum-free medium (SFM) by immunoblotting and positively identified as IGFBP-2 and -3, respectively. 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 tamoxifen-resistant lines. There was no clear correlation between patterns of IGFBP secretion and IGF-I receptor expression.