The specific binding of estradiol and estrone and the subsequent distribution of estrogen-receptor complexes within MCF-7 human breast cancer cells.

We have examined the specific binding of estradiol (E2) and estrone (E1) within MCF-7 cells using both cytosol and whole cell suspension binding assay techniques. The results of these studies have revealed that each of these estrogens binds the high but different affinity to the same single class of cytosol receptor (ER). The incubation of intact cells with E2 at 37 degrees resulted in the rapid formation, nuclear binding, and nuclear processing of E2-ER complexes. Reduction of incubation temperature to 15 degrees C and 4 degrees C resulted in slowed but continued E2-ER formation and nuclear binding, and in a marked inhibition of nuclear receptor processing. The incubation of intact cells with E1 at 37 degrees also was associated with the formation, nuclear binding, and nuclear processing of estrogen-ER complexes. Interestingly, however, E2 rather the E1 represented the major species of specifically bound estrogen under these conditions. This observation suggests that the estrogenic action of E1 in MCF-7 cells may be mediated largely by the intracellular formation of E2. This phenomenon provides a likely explanation of the unexpected potency of E1 in this system previously observed by other workers. Furthermore, our results suggest that E1 may represent a major source of estrogenic stimulation for some hormone-dependent human breast tumors.