Estrogen-like Effects of Tamoxifen on Human Endometrial Carcinoma Transplanted into Nude Mice1

The effect of tamoxifen (TAM) on human endometrii carci noma was investigated in nude mice bearing an estrogen recep tor-positive or estrogen receptor-negative tumor. The receptornegative tumor grew rapidly, and the rates of tumor growth of 17/3-estradiol or TAM-treated animals were identical to the rate of controls. The estradici receptor and progesterone receptor (PR) concentrations in the tumor cytosol remained undetectable under all experimental conditions. In contrast, the rate of growth of steroid receptor-positive tumor was significantly accelerated in the presence of TAM compared to controls (p < 0.02). The increased tumor growth rate was, however, significantly lower (p < 0.01) than that observed in animals receiving 17/3-estradiol. The PR concentration in these tumors was elevated in response to TAM treatment. That the TAM-induced PR was indeed func tional was evident from (a) increased activities of the progestinsensitive enzyme, 17/3-estradiol hydroxysteroid dehydrogenase and (b) histolÃ3gica! appearance of subnuclear vacuolization in these tumors after progestin administration. These studies indi cate that continuous, short-term administration of TAM to nude mice results in an estrogen-like effect on endometrial carcinoma. Based on the finding that TAM induces functional PR, we predict that steroid receptor-positive endometrial carcinoma may show a greater response rate to combined, long-term treatment with TAM and progestin.