Steroid binding properties of estradiol receptors in human breast cancer

The incidence of a specific estradiol receptor among the Finnish breast cancer patients was investigated using methods involving dextran-coated charcoal or sucrose density gradient centrifugation techniques. An estradiol receptor was detected in 20 (71%) out of the 28 tumor specimens studied with the following binding site concentrations: 100-1000 fmoles/mg cytosol protein in 12 patients; 10-99 fmoles/mg cytosol protein in 6 patients and below 10 fmoles/mg cytosol protein in 2 patients the lowest detectable level being about 5 fmoles/mg cytosol protein. The apparent intrinsic association constant of the receptor for estradiol-17 beta ranged from 0.4-32 X 10(10) liters/mole in different breast cancer specimens. Estradiol receptor concentration did not seem to correlate well with the age of the patients or the microscopic structure of the tumor. The ligand-binding specificity of the receptor was studied with 25 different estrogen derivatives in 6 separate tumor specimens. The binding proteins in all these tumors showed very similar ligand specificities, despite differences in their histological types and estradiol-binding site concentrations. The phenolic hydroxyl group at C--3 was essential for an effective binding by the receptor, whereas certain modifications in the D-ring structure were well tolerated. As is the case with other steroid receptors, certain hydrophobic substituents seemed to increase the binding of the ligand by the breast cancer estradiol receptor. The in vitro binding affinity and the in vivo biological (estrogenic) potency of some of the steroids investigated did not correlate very well.