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Review
. 2015 Aug;7(5):847-62.
doi: 10.2217/epi.15.10. Epub 2015 Feb 17.

Role of epigenetic modifications in luminal breast cancer

Hany A Abdel-Hafiz  1 , Kathryn B Horwitz  1   2
Affiliations
Review

Role of epigenetic modifications in luminal breast cancer

Hany A Abdel-Hafiz et al. Epigenomics. 2015 Aug.

Abstract

Luminal breast cancers represent approximately 75% of cases. Explanations into the causes of endocrine resistance are complex and are generally ascribed to genomic mechanisms. Recently, attention has been drawn to the role of epigenetic modifications in hormone resistance. We review these here. Epigenetic modifications are reversible, heritable and include changes in DNA methylation patterns, modification of histones and altered microRNA expression levels that target the receptors or their signaling pathways. Large-scale analyses indicate distinct epigenomic profiles that distinguish breast cancers from normal and benign tissues. Taking advantage of the reversibility of epigenetic modifications, drugs that target epigenetic modifiers, given in combination with chemotherapies or endocrine therapies, may represent promising approaches to restoration of therapy responsiveness in these cases.

Keywords: breast cancer; epigenetic modifications; estrogen receptors; progesterone receptors.

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Conflict of interest statement

Financial & competing interests disclosure

The authors are grateful for support from the NIH (RO1-CA026869-35), the Breast Cancer Research Foundation and the National Foundation for Cancer Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Regulation of gene transcription by epigenetic modifications in breast cancers.
Methylation of histone H3 lysine 4 (H3K4), H3K36 or H3K79 is associated with open chromatin and active transcription. Methylation of H3K9, H3K20 or H3K27 is associated with closed chromatin and gene silencing. Histone methylation is regulated by several enzymes that are overexpressed in breast cancer, for example, LSD1, EZH2, G9a and SYMD3. DNA is methylated by DNMTs. MBDs bind to methylated cytosine and form a complex with SIN3A and HDAC leading to chromatin compaction and gene silencing. Histone acetylation is regulated by HDACs and HATs. HATs acetylate histone, relax chromatin and allow transcription factor binding and enhanced transcription. HDAC overexpression has been reported in breast cancers and the use of HDAC inhibitors, trichostatin A or vorinostat, may represent promising approaches to restoration of endocrine responsiveness. Examples of agents used in experimental or clinical trials with promising results are shown. Ac: Acetylation; Me: Methylation. Modified with permission from [9] © BioMed Central Ltd (2011).
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