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 receptors (IGFR) by the ZR-75-1 human breast cancer cell line and tamoxifen-resistant (ZR-75-9a1) and oestrogen-independent (ZR-PR-LT) variants. ZR-75-1 cells expressed 6633+/-953 receptors per cell,(K(d) 0.24+/-0.06 nM). IGFR expression was reduced in ZR-75-9a1 cells (1180+/-614 receptors per cell, K(d) 0.13+/-0.05) and increased in the ZR-PR-LT cell line (18 430+/-3210 receptors per cell, K(d) 0.24+/-17). A comparison of these data with previously published findings for epidermal growth factor 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 changes in IGFR expression observed are associated with changes in steroid hormone receptor status, we also investigated the effects of oestradiol, the synthetic progestin ORG 2058 and dexamethasone on IGFR expression. Oestradiol increased IGFR expression only in the ZR-75-1 cell line. Low concentrations of ORG 2058 increased IGFR levels in the two cell lines positive for progesterone receptor (ZR-75-1 and ZR-PR-LT). High concentrations of ORG 2058 increased IGFR expression in all cell lines, as did dexamethasone. These data suggest that EGFR and IGFR expression may be linked in breast cancer, and that EGFR/IGFR ratios in breast cancer may be a more sensitive prognostic indicator than EGFR expression alone. Regardless of basal IGFR expression by the cell studied, ORG 2058 increased IGFR expression, possibly via both the progesterone and glucocorticoid receptors.
van den Berg
H W
HW
Department of Therapeutics and Pharmacology, The Queen's University of Belfast, UK.
Claffie
D
D
Boylan
M
M
McKillen
J
J
Lynch
M
M
McKibben
B
B
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D066246:ErbB Receptors / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007700:Kinetics; D011282:Pregnenediones / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D011282:Pregnenediones; D045167:Progesterone Congeners; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1