Abstract
DNA hypermethylation and histone modifications are two critical players involved in epigenetic regulation and together play an important role in silencing tumor-suppressor genes in all cancers, including breast cancer. One of the major challenges facing breast cancer researchers is the problem of how to identify critical genes that are epigenetically silenced early in cancer initiation as these genes provide potential early diagnostic and/or therapeutic targets for breast cancer management. This review will focus on compelling evidence that normal Human Mammary Epithelial Cells (HMECs) that escape senescence in culture mimic genetic and epigenetic events occurring in early breast cancer, and provide a valuable system to delineate the early steps in epigenetic deregulation that often occur during transition of a normal breast cell to a premalignant cell. In particular, this model system has been used to investigate the relationship between gene silencing, DNA methylation, histone modifications, and polycomb association that may occur early in oncogenic transformation.
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Abbreviations
- bp:
-
base pairs
- BMI-1:
-
B lymphoma Mo-MLV insertion region
- BRCA1 :
-
breast cancer 1, early onset
- CDKN2A :
-
cyclin dependent kinase inhibitor 2A
- ChIP:
-
chromatin immunoprecipitation
- Cox-2 :
-
cyclo-oxygenase 2
- DNA:
-
deoxyribonucleic acid
- DNMT:
-
DNA methyltransferase
- EZH2:
-
enhancer of zeste homolog 2
- H:
-
histone
- HDAC:
-
histone deacetylase
- HMEC:
-
human mammary epithelial cells
- HMT:
-
histone methyltransferase
- K:
-
lysine
- kb:
-
kilobases
- MBD:
-
methyl-C binding domain
- MeCP2:
-
methyl CpG binding protein 2
- PcG:
-
polycomb group
- PRC:
-
polycomb repressive complex
- Rb :
-
retinoblastoma 1
- SUZ12:
-
suppressor of zeste 12
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Acknowledgments
RAH is supported by a Dora Lush Biomedical Postgraduate Scholarship from the National Health and Medical Research Council (NH&MRC) and in part by a Cancer Institute NSW (CI NSW) Research Scholar Award and a National Breast Cancer Foundation (NBCF) Excellence Award. SJC is supported by an NH&MRC fellowship and NH&MRC project grants.
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Hinshelwood, R.A., Clark, S.J. Breast cancer epigenetics: normal human mammary epithelial cells as a model system. J Mol Med 86, 1315–1328 (2008). https://doi.org/10.1007/s00109-008-0386-3
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DOI: https://doi.org/10.1007/s00109-008-0386-3