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

Department of Human Oncology [M. M. G., S. P. R., V. C. J.], University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792, and Department of Obstetrics and Gynecology [P. G. S.], Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033

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, EnCa101, was stimulated to grow by TAM either alone or when combined with estradiol. This contrasted with the non-stimulation of the breast tumor, MCF-7, by TAM alone and the antagonist 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 dictate tissue response. The conclusion is supported by the finding of very similar patterns of metabolites in the two tumors after administration of [ring-³H]TAM. 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 EnCa101 tumors than control (42 ± 5 fmol/mg cytosol protein) and increased further with combined treatment (485 ± 75 fmol/mg cytosol protein). Estrogen receptor 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 estrogen 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 EnCa101 tumor. Overall, these findings suggest that the disparate pharmacology of TAM is a tissue-specific phenomenon.

¹ Supported in part by USPHS Grants P01 CA-20432 and R01 CA-32713 (V. C. J.), the generosity of the Anderson fund of the Wisconsin Clinical Cancer Center (V. C. J.), and National Cancer Institute Grant P01 CA-40011 (P. G. S.).

² To whom requests for reprints should be addressed, at Dept. of Human Oncology, University of Wisconsin Clinical Cancer Center, 600 Highland Avenue, Madison, WI 53792.

Received 8/11/87. Revised 10/27/87. Accepted 11/13/87.

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