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The Effects of Estrogens and Antiestrogens on Hormone-responsive Human Breast Cancer in Long-Term Tissue Culture¹

Medicine Branch, National Cancer Institute, Bethesda, Maryland 20014

We have established or characterized six lines of human breast cancer maintained in long-term tissue culture for at least 1 year and have examined these lines 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 strongly inhibitory, and at concentrations greater than 3 x 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 17ß-estradiol or diethylstilbestrol exceeding 10^-7 M. Killing by high concentrations of estrogen is probably a nonspecific effect in that we observe this response with 17-estradiol at equivalent concentrations and in the otherwise unresponsive cells that contain no estrogen receptor sites.

¹ This is Paper 1 of a series on hormon-responsive human breast cancer cell lines in long-term tissue culture.

Received 11/11/75. Accepted 9/10/76.

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