EFFECTS OF ESTROGENS AND ANTIESTROGENS ON HORMONE-RESPONSIVE HUMAN BREAST-CANCER IN LONG-TERM TISSUE-CULTURE

Abstract

Six lines of human breast cancer maintained in long-term tissue culture for at least 1 yr were established or characterized, and these lines were examined for estrogen responsiveness. One of these cell lines, MCF-7, shows marked stimulation of macromolecular synthesis and cell division with physiological concentrations of estradiol. Antiestrogens are inhibitory, and at concentrations greater than 3 .times. 10-7 M they kill cells. Antiestrogen effects are prevented by simultaneous treatment with estradiol or reversed by addition of estradiol to cells incubated in antiestrogen. Responsive cell lines contain high affinity specific estradiol receptors. Antiestrogens compete with estradiol for these receptors but have a lower apparent affinity for the receptor than estrogens. Stimulation of cells by estrogens is biphasic, with inhibition and cell death at concentrations of 17 .beta.-estradiol or diethylstilbestrol exceeding 10-7 M. Killing by high concentrations of estrogen is probably a nonspecific effect in that this response was observed with 17 .alpha.-estradiol at equivalent concentrations and in the otherwise unresponsive cells that contain no estrogen receptor sites.