Estrogenic Effects of Nafoxidine on Ovarian-Dependent and Independent Mammary Tumor Lines in the Mouse

Nafoxidine (1-[2-[p-(3, 4-dihydro-6-methoxy-2-phenyl-1 -naphthy 1) phenoxy]ethy 1] -pyrrolidine hydrochloride); a triphenylethylene derivative] and estradiol cause translocation of the estrogen receptor to the nucleus, elevate the levels of cytoplasmic progesterone receptors, and do not affect levels of nuclear progesterone receptor in hormone-dependent and -independent MXT-3590 mammary tumor lines. Cytoplasmic and nuclear receptor levels were measured by the dextran-coated charcoal assay and a modified protamine sulfate nuclear exchange assay, respectively. Both estradiol (2.5 μg) and nafoxidine (40 μg) stimulate partial growth in the independent line. These data are the first evidence of the estrogenic effects of a so-called antiestrogen (nafoxidine) on the quantity of progesterone receptors in a hormone-independent experimental mammary tumor. The growth effects of antiestrogens demonstrated here in ovariectomized mice should alert clinicians to be watchful of these effects when using such ds in the treatment of human breast cancer. These results also confirm recent suggestions that growth and progesterone receptor synthesis are controlled separately by estrogenic compounds.