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

Autor: Pitta CA; University of Cyprus, Department of Biological Sciences, Lefkosia, Cyprus., Papageorgis P, Charalambous C, Constantinou AI
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2013 Sep 01; Vol. 337 (2), pp. 167-76. Date of Electronic Publication: 2013 Jun 07.
DOI: 10.1016/j.canlet.2013.05.031
Abstrakt: 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.
(Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: