Estradiol Binding to Nuclear Receptors in Human Breast Cancer Tissue (MCF-7 Cell Line) and in Dimethylbenz(a)anthracene-Induced Mammary Carcinoma*

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Abstract
Nuclear estradiol receptors were measured in human breast carcinoma tissue (cell line MCF-7) and in DMBA [dimethylbenz[a]anthracene] induced rat mammary carcinoma. Receptor degradation by intracellular proteases was avoided by repeated washing of the particulate-bound receptor. The amount of occupied nuclear receptors (bound by endogenous estrogen) could be measured be exchange at 30.degree. C, and the amount of unoccupied receptors could be measured at 4 C. Receptors were measured by a single saturating dose of 7.5 nM [3H]estradiol with or without a 100-fold excess of diethylstilbestrol to estimate the amount of nonspecific binding. In mammary tumors from castrated rats, unoccupied receptors were found in the cytoplasm. In the nucleus, neither occupied nor unoccupied receptors could be detected. Thirty min after injection of estradiol, unoccupied estradiol receptors were no longer detected in the cytoplasm. However, 35-50% of the amount of cytoplasmic receptors detected in the castrated rats were found as occupied nuclear receptors. MCF-7 cells before exposure to estradiol contained only unoccupied nuclear and cytoplasmic receptors. After 1-h exposure to estradiol, only occupied nuclear receptors were found. The total amounts of receptors before and after treatment were similar. Nuclear and cytoplasmic estradiol receptors were measured in 44 human breast tumors. Ten tumors contained neither cytoplasmic nor nuclear receptors. In 29 out of 34 patients whose tumors contained cytoplasmic receptors, unoccupied nuclear receptors were present. Occupied nuclear receptors were present. Occupied nuclear receptors were found in 21 out of these 34 tumors, in the younger as well as the older group of patients. The latter contained higher levels of cytoplasmic receptors. The presence of occupied nuclear receptors in those tumors may depend on various factors, including the circulating levels of estradiol, tumor cytoplasmic receptor levels, and translocative ability of the cytoplasmic receptors. [This research has application to breast cancer endocrine therapy].

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