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Effects of Estrone, Estradiol, and Estriol on Hormone-responsive Human Breast Cancer in Long-Term Tissue Culture¹

MecMedical Breast Cancer Service, Medicine Branch, National Cancer Institute, Bethesda, Maryland 20014

The effects of estrone, estradiol, and estriol on MCF-7 human breast cancer are compared. In this estrogen-responsive cell line, all three 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 either estrone or estradiol. All three steroids bind to a high-affinity estrogen receptor found in these cells. The apparent dissociation constant is lower for estradiol than for estrone and estriol, but all three bind to an equal number of sites when saturating concentrations are used. Tritiated estrogens used in binding studies were shown to be radiochemically pure. We conclude that estriol can bind to estrogen receptor and stimulate human breast cancer in tissue culture. Our data do not support an antiestrogenic role for estriol in human breast cancer.

¹ This is Paper 5 in a series on the effects of hormones on human breast cancer cell lines in tissue culture.

Received 12/13/76. Accepted 3/14/77.

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