title: Minireview: The Link Between ERα Corepressors and Histone Deacetylases in Tamoxifen Resistance in Breast Cancer.
abstract: Approximately 70% of breast cancers express the estrogen receptor (ER)α and are treated with the ERα antagonist, tamoxifen. However, resistance to tamoxifen frequently develops in advanced breast cancer, in part due to a down-regulation of ERα corepressors. Nuclear receptor corepressors function by attenuating hormone responses and have been shown to potentiate tamoxifen action in various biological systems. Recent genomic data on breast cancers has revealed that genetic and/or genomic events target ERα corepressors in the majority of breast tumors, suggesting that the loss of nuclear receptor corepressor activity may represent an important mechanism that contributes to intrinsic and acquired tamoxifen resistance. Here, the biological functions of ERα corepressors are critically reviewed to elucidate their role in modifying endocrine sensitivity in breast cancer. We highlight a mechanism of gene repression common to corepressors previously shown to enhance the antitumorigenic effects of tamoxifen, which involves the recruitment of histone deacetylases (HDACs) to DNA. As an indicator of epigenetic disequilibrium, the loss of ERα corepressors may predispose cancer cells to the cytotoxic effects of HDAC inhibitors, a class of drug that has been shown to effectively reverse tamoxifen resistance in numerous studies. HDAC inhibition thus appears as a promising therapeutic approach that deserves to be further explored as an avenue to restore drug sensitivity in corepressor-deficient and tamoxifen-resistant breast cancers.
authors: Division of Experimental Medicine, Department of Oncology and Surgery, Segal Cancer Center, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montréal, Québec, Canada H3T 1E2.
authors: Stéphanie
authors: S
authors: Légaré
authors: Division of Experimental Medicine, Department of Oncology and Surgery, Segal Cancer Center, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montréal, Québec, Canada H3T 1E2.
authors: Mark
authors: M
authors: Basik
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D051837:COUP Transcription Factor II / Q000378:metabolism; D005260:Female; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D056971:Nuclear Receptor Co-Repressor 1 / Q000378:metabolism; D056985:Nuclear Receptor Co-Repressor 2 / Q000378:metabolism; D000078723:Nuclear Receptor Interacting Protein 1; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051837:COUP Transcription Factor II; D036961:Matrix Attachment Region Binding Proteins; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D000078723:Nuclear Receptor Interacting Protein 1; D013629:Tamoxifen; D006655:Histone Deacetylases