Contrasting Actions of Tamoxifen on Endometrial and Breast Tumor Growth in the Athymic Mouse1

The effects of the antiestrogen tamoxifen (TAM) on the growth of two hormone-sensitive human tumors have been examined in athymic mice. The endometrial tumor, EnCalOl, was stimulated to grow by TAM either alone or when combined with estradiol. This contrasted with the nonstimulation of the breast tumor, MCF-7, by TAM alone and the antago nist action of TAM on estradiol-stimulated growth of MCF-7 tumors. The individual tumor responses were observed even when the two tumor types were implanted on opposite sides of the same animal. This suggests that host metabolism of TAM does not dictât«* tissue response. The conclusion is supported by the finding of very similar patterns of metab olites in the two tumors after administration of Ir/n^-'I I] I AM. Tissue metabolism therefore is unlikely to be involved. Progesterone receptor levels were higher in estradiol (376 ±35 fmol/mg cytosol protein)or TAM (317 ±37 fmol/mg cytosol protein)-stimulated EnCalOl tumors than control (42 ±5 fmol/mg cytosol protein) and increased further with combined treatment (485 ±75 fmol/mg cytosol protein). Estrogen recep tor levels, however, were lower in estradiol (45 ±11 fmol/mg cytosol protein)-treated tumors than control (92 ±13 fmol/mg cytosol protein) but higher than control in TAM (200 ±15 fmol/mg cytosol protein)treated tumors. Tumors grown with estradiol and TAM had lower estro gen receptor levels (130 ±7 fmol/mg cytosol protein) than tumors grown with TAM alone. Estrogen receptor levels indicate that TAM may not be acting exactly as estradiol in the EnCalOl tumor. Overall, these findings suggest that the disparate pharmacology of TAM is a tissuespecific phenomenon.