Functionality of estrogen receptor and tamoxifen treatment of R3327 Dunning rat prostate adenocarcinoma.
The functionality of the estrogen receptor as determined by the effect of estrogen on progesterone receptor levels and the effect of tamoxifen on tumor growth has been examined in the R3327 Dunning rat prostate adenocarcinoma. The progesterone receptor was absent in 78% of prostate tumors grown in male Copenhagen X Fischer F1 rats but was induced in tumors taken from rats given injections of 25 microgram estradiol benzoate per kg for 10 days. This result suggested that the tumor might be sensitive to the antiestrogen tamoxifen, and it was subsequently shown that treatment of rats with tamoxifen (0.5 mg/kg) 5 times/week for 2 to 7 months resulted in marked suppression of tumor growth in 91% of the tumors examined. In vitro binding analysis demonstrated that tamoxifen competed for the estrogen receptor in the tumor but not for the androgen receptor. These data suggest that tamoxifen might be acting directly on the tumor, although an indirect effect cannot be ruled out, since plasma testosterone levels were reduced as a result of tamoxifen treatment. Regulation of androgen and estrogen receptors was also observed in this tumor system. Thus, administration of estradiol benzoate for 10 days resulted in increased levels of androgen receptor with no change in estrogen receptor. Long-term tamoxifen treatment had a similar effect. Short-term castration, which appeared to induce the progesterone receptor, also resulted in increased levels of both androgen and estrogen receptors. This latter observation suggests that tamoxifen might be even more effective in castrated rats.