Reversal of ER-β silencing by chromatin modifying agents overrides acquired tamoxifen resistance

Chara A. Pitta, Panagiotis Papageorgis, Christiana Charalambous, Andreas I. Constantinou

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

The purpose of this work is to determine the molecular mechanisms underlying tamoxifen resistance. We show here that ER-β is epigenetically silenced in a cell line with acquired tamoxifen resistance (MCF-7/TAM-R) and this could be reversed by 5-AZA-deoxycytidine (5-AZA) and trichostatin-A (TSA) pre-treatment. Subsequent treatment with 4-hydroxy-tamoxifen (4-OHT) induced ER-β nuclear translocation, upregulated pS2 and p21 levels and reduced cell viability. Transfection with an ER-β expression vector sensitized MCF-7/TAM-R cells to the growth inhibitory and pro-apoptotic effects of 4-OHT, indicating that ER-β re-expression alone is sufficient to restore sensitivity to tamoxifen. This novel finding reveals that ER-β is fundamental in overcoming acquired tamoxifen resistance and provides insights for new therapeutic protocols against breast cancer.

Original languageEnglish
Pages (from-to)167-176
Number of pages10
JournalCancer Letters
Volume337
Issue number2
DOIs
Publication statusPublished - 1 Sep 2013

Keywords

  • 4-OHT
  • 5-AZA
  • Breast cancer
  • DNMT
  • E
  • Epigenetics
  • ER-α
  • ER-β
  • Estrogen receptors
  • HDAC
  • MTT
  • SERMs
  • Tamoxifen resistance
  • TSA

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