Human estrogen receptor-α (ER-α) transactivation by selective estrogen receptor modulators (SERMs) on VIT regulatory region in ER-α-negative breast cancer cell line Evsa-T transiently transfected by ER-α

The action of 11 selective estrogen receptor modulators (SERMs) was investigated in two breast cancer cell lines, the estrogen receptor-α-positive (ER-α⁺) MCF-7 and the ERα- Evsa-T.

Our experiments were conducted by transient transfection of these cells by a reporter plasmid carrying the luciferase gene under the transcriptional control of the minimal promoter tk and the regulatory region of vitellogenin A1 gene (Vit-tk-Luc). This latter region is known to include a perfect estrogen responsive element (ERE). Evsa-T cells were cotransfected with an expression vector for the human ER-α.

Estradiol (E₂) always increased transcription of Vit-tk-Luc basal activity in both cell lines. Pure antiestrogens repressed it in MCF-7 cells, and had no effect in Evsa-T cells. Interestingly, in Evsa-T cells as compared with MCF-7 cells, SERMs for which the chemical structure contain clusters that mimic hydrophobic substituents linked to the 11β-position of estradiol conferred greater transcription. Of note, deletion of one half of the ERE site did not affect transcription in Evsa-T cells, but abrogated it in MCF-7 cells. Moreover, substitution of Vit by an AP-1 site failed to activate transcription in each case.

Our results show that some SERMs may act as strong agonists on transcription mediated by transfected ER-α in ER-α^- breast tumors with poor prognosis for antihormone therapy. We speculate that additional binding sites for transcription factors, as well as different coactivators, would be involved in this enhancement of activity.