EFFECTS OF ESTRONE, ESTRADIOL, AND ESTRIOL ON HORMONE-RESPONSIVE HUMAN BREAST-CANCER IN LONG-TERM TISSUE-CULTURE

Abstract

The effects of estrone, estradiol and estriol on MCF-7 human breast cancer are compared. In this estrogen responsive cell line, all 3 estrogens are capable of inducing equivalent stimulation of amino acid and nucleoside incorporation. Estriol is capable of partially overcoming antiestrogen inhibition with tamoxifen (ICI 46474), even when antiestrogen is present in 1000-fold excess. Antiestrogen effects are completely overcome by 100-fold less estriol. Studies of metabolism of estrogens by MCF-7 cells revealed no conversion of estriol to estrone or estradiol. All 3 steroids bind to a high affinity estrogen receptor found in these cells. The apparent Kd is lower for estradiol than estrone and estriol, but all 3 bind to an equal number of sites when saturating concentrations are used. 3H-Estrogens used in binding studies were radiochemically pure. Estriol can bind to estrogen receptor and stimulate human breast cancer in tissue culture. The data do not support an antiestrogenic role for estriol in human breast cancer.