Journal
JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 86, Issue 12, Pages 1315-1328Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00109-008-0386-3
Keywords
Human mammary epithelial cells; Breast cancer; DNA methylation; Histone modifications; Biomarkers
Funding
- National Health and Medical Research Council (NHMRC)
- Cancer Institute NSW (CI NSW) Research Scholar Award
- National Breast Cancer Foundation (NBCF)
- NHMRC
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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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