Enhanced Growth of an Estrogen Receptor-negative Endometrial Adenocarcinoma by Estradici in Athymic Mice1

The aim of this study was to investigate the effects of estradici and tamoxifen (I AM) on the growth of human endometrial carcinomas in athymic mice. Tissues from primary tumors were implanted into estradiol-treated mice. In passage 2, animals were treated with (a) placebo, (Ã ̈)estradici, (e) estradici plus TAM, and (d) TAM alone. The size of the tumors was measured weekly. Estrogen receptors (ER) were deter mined with the dextran-coated charcoal method and/or ER enzyme-linked immunoassay. Progesterone receptors were measured with the dextrancoated charcoal technique. Of 16 primary tumors, 2 grew in the athymic mice and were studied further. Tumor EL was positive for ER (145 Inni]/ mg protein) and progesterone receptors (993 fmol/mg protein). Tumor EL in passage 2 was not significantly stimulated by estradici, but was stimulated by a combination of estradici and TAM. Treatments (estradici, estradici plus TAM, or TAM) all increased tumor growth in passage 3. Tumor BR and a metastasis BR-MET were ER and progesterone receptor negative, applying dextran-coated charcoal, ER enzyme-linked immu noassay, and immunocytochemistry. The BR and BR-MET cells contain the complete ER gene but do not express any measurable amounts of ER mRNA as quantitated by Northern blot analysis, using a complete ER complementary DNA probe. In all animal passages the growth rate was significantly higher in estradiol-treated mice compared with the control. TAM alone had some growth stimulatory effect, but much smaller than observed in the estradici group. TAM inhibited estradiol-stimulated growth. These results suggest that estradici and possibly TAM are capable of stimulating tumor growth in the athymic mice independently from ER, potentially through a host-mediated mechanism.