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  • Meeting abstract
  • Open Access

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

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Breast Cancer Research20013 (Suppl 1) :A45

  • Received: 10 May 2001
  • Published:


  • Estrogen
  • Estradiol
  • Breast Cancer Cell Line
  • Regulatory Region
  • Selective Estrogen Receptor Modulator

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.

Authors’ Affiliations

Laboratoire J-C Heuson de Cancérologie Mammaire, Institut Jules Bordet, Brussels, Belgium


© BioMed Central Ltd 2001