High affinity cytosol binding site(s) for antiestrogens in two human breast cancer cell lines and in biopsy specimens devoid of estrogen receptors.

It is known from previous investigations by other authors that the non-steroidal molecule Tamoxifen competes for estradiol binding sites in target tissues and displays partial agonist-antagonist effects. It is able to bind a cytosol protein distinct from ER which has been detected in target tissues, as well as in fetal target and non-target organs. The present work investigates the antiestrogen binding activity of human breast cancer cell lines and tumor biopsies. It is found that BT-20 and MDA-MB 231 cell lines devoid of ER and PGR contain a cytosol protein component able to bind antiestrogens with a high affinity (= 2 X 10(-9) M). The 3H-labeled complex prepared in hypotonic buffer sediments at 6.25 S in a sucrose gradient. A substantial amount of antiestrogen binding sites is found to be linked to the microsomal cell fraction, in agreement with previous data from other investigators. In experiments using whole cells incubated at 37 C, the complex is depleted from the cytosol compartment. A low amount of radioactivity is extracted from the purified nuclei. In the cytosol of human breast tumor biopsies the presence of antiestrogen binding sites is not exclusively associated with the presence of ER and PGR. The identity of the natural ligand which binds to these sites under physiological conditions merits investigation.