Specific estrogen-binding capacity of the cytoplasmic receptor in normal and neoplastic breast tissues of humans.

Abstract

Carcinomas and nonmalignant breast tissues from 89 women undergoing surgery were examined for the presence of specific estrogen-binding substances by a radioligand binding technique in vitro . Following incubation of the 105,000 × g supernatant fraction with estradiol-17β-6,7-3H of high specific radioactivity, in the presence or absence of a known antiestrogen, specific receptors for estra-1,3,5,(10)-triene-3,17β-diol-3H were identified by isotopic profiles from sucrose gradient analyses. Cytoplasmic estrogen receptors from breast carcinoma migrated with a sedimentation velocity coefficient of approximately 8 to 9 S. Cytosols from 29 primary carcinomas were classified as positive, exhibiting an average binding capacity of 43.0 ± 5.3 fmoles/mg protein, with a range of 10.3 to 137.6 fmoles/mg protein. An additional 10 carcinomas were considered borderline on the basis of an average binding capacity of 5.6 ± 0.4 fmoles/mg protein, with a range of 3.3 to 7.4 fmoles/mg protein. Thirty-six of 75 tumors displayed insignificant specific estrogen binding. Inhibition of hormone binding by the competitive inhibitor, CN-55,945-27, averaged 87 ± 3% for the tumor cytosols exhibiting elevated binding; specific binding by cytosols with low receptor capacity was inhibited by 81 ± 5%. In addition to these neoplasms, 16 specimens of normal breast, 5 of fibrocystic disease, and 1 of fibroadenoma were analyzed; all but one of these exhibited insignificant specific binding. These data confirm the presence of specific estrogen-binding substances in certain infiltrating ductal carcinomas of the human breast. Twenty-three of the 29 carcinomas exhibiting specific estra-1,3,5,(10)-triene-3,17β-diol-binding capacity were from postmenopausal women 55 years of age or older. Specific estra-1,3,5,(10)-triene-3,17β-diol-binding capacity of a tumor was apparently not related to the presence of metastases, nor was it related to the estimated percentage of carcinoma cells in the specimen examined.