| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2116268 | Cancer Letters | 2013 | 10 Pages |
•ER-β is silenced in MCF-7 cells with acquired tamoxifen resistance.•Treatment with the 5-AZA/TSA re-sensitizes cells to the inhibitory effects of 4-OHT.•Transfection with an ER-β expression vector sensitized resistant cells to 4-OHT.•ER-β re-expression alone is sufficient to restore sensitivity to tamoxifen.
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.
