Regulation of epidermal growth factor-receptor by estrogen and antiestrogen in the human breast cancer cell line MCF-7.
Regulation of breast tumor proliferation depends in a large part on a variety of hormones and growth factors. In this report we show that estrogen and antiestrogen modulate epidermal growth factor-receptor (EGF-R) level in the human breast cancer MCF-7 cells with opposite mechanisms. Although a short-term treatment (24h to 48h) with estradiol leads to a decrease in EGF-R number, the addition of hormone in cell culture for 5 days increases EGF-R level with a maximal effect observed at 10(-10) M estradiol. In contrast, when cells are treated with the antiestrogen hydroxytamoxifen, a dose-dependent decrease in EGF-R level occurs. We also report that EGF is able to induce estrogen receptors and, to a lesser extent, progesterone receptors when added to MCF-7 cell cultures. These results demonstrate an interaction between both estrogen receptor and EGF receptor growth promoting systems in target cells. The implications of such an interaction in the understanding of human breast cancer hormone responsiveness and, in the development of therapies, are discussed.
Berthois
Y
Y
Laboratoire Invasion-Métastase - UA CNRS 1175 - Faculté de Médecine - Secteur Nord, Marseille, France.
Dong
X F
XF
Martin
P M
PM
D001943:Breast Neoplasms / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D004815:Epidermal Growth Factor; D066246:ErbB Receptors