EXPRESSION OF RECEPTORS FOR EPIDERMAL GROWTH-FACTOR AND INSULIN-LIKE GROWTH-FACTOR-I BY ZR-75-1 HUMAN BREAST-CANCER CELL VARIANTS IS INVERSELY RELATED - THE EFFECT OF STEROID-HORMONES ON INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR EXPRESSION

We have investigated the expression of insulin-like growth factor I re ceptors (IGFR) by the ZR-75-1 human breast cancer cell line and tamoxi fen-resistant (ZR-75-9al) and oestrogen-independent (ZR-PR-LT) variant s. ZR-75-1 cells expressed 6633+953 receptors per cell (K-d 0.24+/-0.0 6 nM). IGFR expression was reduced in ZR-75-9a1 cells (1180+/-614 rece ptors per cell, K-d 0.13+/-0.05) and increased in the ZR-PR-LT cell li ne (18 430+/-3210 receptors per cell, K-d 0.24+/-17). A comparison of these data with previously published findings for epidermal growth fac tor receptor (EGFR) expression by these cell lines revealed that IGFR and EGFR expression are inversely related in the variant lines whereas ZR-75-1 cells express similar numbers of both receptors. Since the ch anges in IGFR expression observed are associated with changes in stero id hormone receptor status, we also investigated the effects of oestra diol, the synthetic progestin ORG 2058 and dexamethasone on IGFR expre ssion. Oestradiol increased IGFR expression only in the ZR-75-1 cell l ine. Low concentrations of ORG 2058 increased IGFR levels in the two c ell lines positive for progesterone receptor (ZR-75-1 and ZR-PR-LT). H igh concentrations of ORG 2058 increased IGFR expression in all cell l ines, as did dexamethasone. These data suggest that EGFR and IGFR expr ession may be linked in breast cancer, and that EGFR/IGFR ratios in br east cancer may be a more sensitive prognostic indicator than EGFR exp ression alone. Regardless of basal IGFR expression by the cell. lines studied, ORG 2058 increased IGFR expression, possibly via both the pro gesterone and glucocorticoid receptors.