AGONISTIC EFFECT OF TAMOXIFEN IS DEPENDENT ON CELL-TYPE, ERE-PROMOTERCONTEXT, AND ESTROGEN-RECEPTOR SUBTYPE - FUNCTIONAL DIFFERENCE BETWEEN ESTROGEN-RECEPTOR-ALPHA AND ESTROGEN-RECEPTOR-BETA

To investigate the functional differences between estrogen receptor (E R) alpha and beta subtypes, we studied the expression and the transcri ption stimulating activities of these receptors. RT-PCR has demonstrat ed that ER alpha is expressed at a high level in MCF-7 cells derived f rom human breast cancer. Both ER alpha and ER beta were expressed at a lower level in HOS-TE85 and Saos2 cells derived from human osteosarco ma. Chloramphenicol acetyltransferase reporter assay detected the tran scriptional activation by the endogenous receptor only in MCF-7 cells. Agonistic effect of tamoxifen was observed as strong as that of 17 be ta-estradiol on ERE activation in MCF-7 cells at the concentration of 10(-7) M when ERE-containing reporter is constructed with beta-globin promoter, The effect of tamoxifen was not apparent when the reporter w as constructed with thymidine kinase promoter, suggesting that the dif ferential gene activation between tamoxifen and estrogen may take plac e depending upon ERE-promoter context. Agonistic activity of tamoxifen was also detected in COS-7 and Saos-2 cells, but not in HEC-1 cells d erived from human endometrial carcinoma via exogenously expressed ER. Interestingly, this effect was ER alpha specific, Thus, Bye demonstrat e that agonistic effect of tamoxifen depends on the cell type, ERE-pro moter context, and ER subtype. These parameters would explain at least a part of the tissue specific effects of antiestrogens in vivo. (C) 1 995 Academic Press.