Dichotomous effects of tamoxifen on a transplantable rat mammary tumor.

The effect of the antiestrogen tamoxifen on growth of the transplantable autonomous mammary tumor MTW-9B was compared with its effects on progesterone and estrogen receptor levels. Growth of the tumor was similar in intact rats, ovariectomized rats, or ovariectomized rats given estradiol, in both the presence and the absence of tamoxifen. Progesterone receptor levels, however, were reduced by ovariectomy and restored by estrogen administration. Tamoxifen antagonized this effect of estrogen, although when administered by itself to ovariectomized rats it acted as an agonist, since progesterone receptor levels were induced. Cytosol estrogen receptor was depleted by tamoxifen in both intact and ovariectomized rats. In uterus from the same animals, tamoxifen also showed both antagonist and agonist properties, although here too there was an apparent dissociation between effects on growth and progesterone receptor levels. We conclude from these experiments that: (a) the estrogen receptor complex may be acting at more than one site on the genome; and (b) regulation of progesterone receptor levels by estrogen (or tamoxifen) does not necessarily predict sensitivity of tumor growth to antiestrogens.