EFFECTS OF TAMOXIFEN ON HUMAN BREAST-CANCER CELLS IN-VITRO

Long-term treatment of the estrogen sensitive human breast cancer cell line EFM-19 with the antiestrogenic compound Tamoxifen resulted in a variant line EFM-19 T, which was stimulated by Tamoxifen. Estrogen rec eptor analysis by radioligand assay (charcoal method), revealed a 2.5 fold higher receptor concentration in EF-19 T cells than in the parent al EFM-19 cell-line. As demonstrated with the immunocytochemical assay (ER-ICA) only 60% of the parental EFM-19 cells were estrogen receptor positive, whereas 98% of the EFM-19 T cells expressed estrogen recept or protein. In addition, receptor content per cell was higher in the T amoxifen treated subline than in the parental cell line. Analogous wit h the growth promoting effect of Tamoxifen on EFM-19 T cells, Tamoxife n acted like estrogen leading to a down regulation of cellular estroge n receptor concentration. The partial growth dependency of the EFM-19 T cells on the presence of Tamoxifen demonstrates estrogenic effects o f Tamoxifen and explains the withdrawal response obtained in the treat ment of breast cancer patients when remission occurs after termination of ineffective treatment with Tamoxifen.