Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice.
The effect of tamoxifen (TAM) on human endometrial carcinoma was investigated in nude mice bearing an estrogen receptor-positive or estrogen receptor-negative tumor. The receptor-negative tumor grew rapidly, and the rates of tumor growth of 17 beta-estradiol or TAM-treated animals were identical to the rate of controls. The estradiol 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 less than 0.02). The increased tumor growth rate was, however, significantly lower (p less than 0.01) than that observed in animals receiving 17 beta-estradiol. The PR concentration in these tumors was elevated in response to TAM treatment. That the TAM-induced PR was indeed functional was evident from (a) increased activities of the progestin-sensitive enzyme, 17 beta-estradiol hydroxysteroid dehydrogenase and (b) histological appearance of subnuclear vacuolization in these tumors after progestin administration. These studies indicate 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.
D000818:Animals; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014594:Uterine Neoplasms / Q000503:physiopathology*
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol