Ariazi, E. A., Taylor, J. C., Black, M. A., Nicolas, E., Slifker, M. J., Azzam, D. J., Boyd, J. (2017) A new role for ERα: Silencing via DNA methylation of basal, stem cell, and EMT genes. Molecular Cancer Research, 15 (2). pp. 152-164. ISSN 1541-7786
Abstract
Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα+) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα+ status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα+ cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression. ERα-dependent DNA methylation targets (n = 39) were enriched for ERα-binding sites, basal-up/luminal-down markers, cancer stem cell, epithelial-mesenchymal transition, and inflammatory and tumor suppressor genes. Kaplan-Meier survival curve and Cox proportional hazards regression analyses indicated that these targets predicted poor distant metastasis-free survival among a large cohort of breast cancer patients. The basal breast cancer subtype markers LCN2 and IFI27 showed the greatest inverse relationship with ERα expression/activity and contain ERα-binding sites. Thus, genes that are methylated in an ERα-dependent manner may serve as predictive biomarkers in breast cancer.
| Item Type: | Paper |
|---|---|
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation |
| CSHL Authors: | |
| Communities: | CSHL labs > Boyd lab |
| Highlight: | Boyd, Jeff |
| Depositing User: | Adrian Gomez |
| Date: | 2017 |
| Date Deposited: | 13 Mar 2020 18:47 |
| Last Modified: | 28 May 2020 21:31 |
| PMCID: | PMC5308451 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/39209 |
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