Displacement by tamoxifen of the estradiol-estrogen receptor binding: A functional assay for breast cancer studies

Abstract

Displacement curves with estradiol (E 2) and Tamoxifen (Tam) of the [ 3H]E 2-ER binding in 49 ER+ mammary neoplasias showed a great heterogeneity suggesting the existence of more than one population of ER+ tumors when the relative binding affinity of both ligands for the ER was considered. The (D 50E 2/D 50Tam) × 100 ratio was called Displacement Index (DI) with values assimetrically distributed from 0.05 to 2.90. The range from 0.18 to 0.54 was adopted as central interval given by the median ±2SE (median: 0.36; SE: 0.09). DI values below 0.18 (24% of the tumors in our series) were considered as “lower”, indicating that higher Tam doses would be necessary to displace the E 2-ER binding. The potency of Tam as displacer is dependent not only of its own affinity for the ER, but also of that of E 2 for the same receptor. The DI expresses their relative binding “strength”. DI values were not correlated with ER and progesterone receptor content nor with the D 50 Tam and D 50E 2 taken separately. Antiestrogen binding sites (AEBS) were determined in the cytosol (AEBS c) and in the microsomal fraction of 10 ER+ tumors from our series. The AEBS c/ER ratio was inversely correlated with the DI, that is, displacement of 3HE 2 from the E 2-ER complex by Tam would be lower in tumors with higher AEBS c/ER ratio. The DI is another parameter to be considered in the study of the sensitivity of breast neoplasias to antiestrogen treatments.