Effect of tamoxifen and tamoxifen derivatives on the conversion of estrone-sulfate to estradiol in the R-27 cells, a tamoxifen-resistant line derived from MCF-7 human breast cancer cells.

R-27 cells, a tamoxifen-resistant clone of MCF-7 mammary cancer cells, were used to study the effect of tamoxifen and its derivatives (4-hydroxytamoxifen, N-desmethyltamoxifen and cis-tamoxifen) on the conversion of estrone sulfate to estradiol. The present data indicate that (1) tamoxifen, 4-hydroxytamoxifen, N-desmethyltamoxifen and cis-tamoxifen inhibit the uptake of the radioactivity after incubation of these triphenylethylene derivatives with [3H]-estrone sulfate; (2) there is a significant decrease of the conversion of estrone sulfate to estradiol by these antiestrogens; (3) the concentrations of estradiol (cytosol + 0.6 M KCl nuclear extract) which are 293 +/- 50 pg/mg DNA in the control studies (estrone sulfate alone), diminish to 26 +/- 5 pg/mg DNA after addition of tamoxifen, to 9 +/- 2 with 4-hydroxytamoxifen, to 24 +/- 7 with N-desmethyltamoxifen and to 32 +/- 6 with cis-tamoxifen. It is concluded that estrone sulfate can play an important role in the biological responses to estrogens in this breast cancer cell line and tamoxifen and its derivatives block the conversion of estrone sulfate to estradiol. The decrease in concentration of estradiol could be explained by the presence of the estrogen receptor system but other ways of the action of antiestrogens remain to be explored.