Biological effects and morphological responses to estriol, estriol-3-sulfate, estriol-17-sulfate and tamoxifen in a tamoxifen-resistant cell line (R-27) derived from MCF-7 human breast cancer cells.

The R-27 cell line is a variant clone derived from the MCF-7 human breast cancer cell line which has lost its inhibitory response to anti-estrogens. In the present study, we have compared the biological responses to estriol (E3), estriol-3-sulfate (E3-3-S), and estriol-17-sulfate (E3-17-S) in these cells and in the parent MCF-7 cells. In the R-27 cell line after 7 days of culture, the progesterone receptor (PR) concentrations were greatly increased by E3 and E3-3-sulfate; however, tamoxifen did not block this effect. The effect in PR provoked by E3-17-S was significantly less intense. The concentrations of PR (pmol/mg DNA +/- S.D.) in the R-27 cells were as follows: control: 1.1 +/- 0.8; +E3: 10.5 +/- 2.4; +E3-3-S: 5.4 +/- 2.3; +E3-17-S: 2.6 +/- 0.8. E3 and E3-3-S also stimulated PR in the MCF-7 cells but to a lesser extent. No stimulation was observed in the E3-17-S treatment. A fraction (0.5-1%) of the E3-3-S was found to be hydrolysed in the medium during the incubation in both cell lines, but no hydrolysis occurred after incubation with E3-17-S. Ultrastructural observations showed that in the E3 and E3-3-S treated cells, there was an important development of the ergastoplasm, bundles of filaments and an accumulation of ribosomes. No significant morphological alteration was observed in cells exposed to E3-17-S. In conclusion, E3 is biologically very active in both the R-27 and the MCF-7 cell lines and E3-3-S could play a role in the control of the estrogenic activity of E3.