Effects of antiestrogens on the estrogen-regulated pS2 RNA and the 52- and 160-kilodalton proteins in MCF7 cells and two tamoxifen-resistant sublines.

Abstract

The effects of estradiol and antiestrogens on two estrogen-regulated proteins (52 and 160 kDa) and an estrogen-inducible mRNA (pS2) have been measured in the MCF7 human breast cancer cell line and two tamoxifen-resistant sublines. In MCF7 cells, tamoxifen (or nafoxidine) alone does not significantly affect pS2 mRNA levels nor transcription of the pS2 gene but completely antagonizes the ability of estradiol to increase pS2 RNA levels. The estrogen-mediated increase in pS2 mRNA levels resembles that of two estrogen-regulated proteins (52 and 160 kDa) that are released from MCF7 cells into the culture medium. This is distinct from the estrogen-mediated increase in progesterone receptor which is also obtained by tamoxifen treatment. In the two tamoxifen-resistant sublines (R27 and RTx6), tamoxifen does not increase pS2 mRNA levels or 160-kDa protein production but increases the production of the 52-kDa protein. These results show that in these tamoxifen-resistant cells, tamoxifen has become fully estrogenic for one, but not all estrogen-regulated responses.