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 language | English |
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Pages (from-to) | 167-176 |
Number of pages | 10 |
Journal | Cancer Letters |
Volume | 337 |
Issue number | 2 |
DOIs | |
Publication status | Published - 1 Sept 2013 |
Keywords
- 4-OHT
- 5-AZA
- Breast cancer
- DNMT
- E
- Epigenetics
- ER-α
- ER-β
- Estrogen receptors
- HDAC
- MTT
- SERMs
- Tamoxifen resistance
- TSA