Changes in insulin-like growth factor-I receptor expression and binding protein secretion associated with tamoxifen resistance and estrogen independence in human breast cancer cells in vitro

Conditioned medium from a series of human breast cancer cell lines representing the phenotypes of estrogen dependence (ZR-75-1, MCF-7), tamoxifen resistance (ZR-75-9a1, LY2) and estrogen independence (ZR-PR-LT) contained four detectable insulin-like growth factor binding proteins (IGFBPs) of MW 24, 34, 44 and 70 kDa. In the tamoxifen resistant lines secretion of the 24 kDa IGFBP was depressed in comparison to the parent lines whilst secretion of the 44 kDa IGFBP was unaffected. Secretion of this species by ZR-PR-LT cells was reduced. Following incubation in medium containing 1% serum both tamoxifen resistant cell lines secreted higher levels of the 44 kDa IGFBP than the respective parent lines. These changes in IGFBP secretion associated with the development of tamoxifen resistance and estrogen independence were accompanied by changes in the expression of receptors for IGF-I.