Endocrine disruption of the epigenome: a breast cancer link
- 1Cancer Drug Discovery, MIMR-PHI Institute of Medical Research, PO BOX 5152, Clayton, Victoria 3168, Australia
2Department of Molecular Biology and Biochemistry, Monash University, Clayton, Victoria, Australia
3Department of Environmental Health, Center for Environmental Genetics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
- Correspondence should be addressed to K C Knower; Email: kevin.knower{at}princehenrys.org
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Figure 1
Endocrine disruptors and risk factors mediate epigenome changes increasing breast cancer risk. EDC may prolong puberty and increase mammary epithelial cell proliferation allowing a longer duration or increased rate of epigenetic remodeling of the developing mammary gland leading to destabilization of chromatin integrity, mispackaging of genes in active/inactive domains and aberrant expression of genes in key regulatory pathways. The susceptibility of the action of EDCs is compounded by associated risk factors such as a high-fat diet. BPA, bisphenol A; DES, diethylstilbestrol; TCDD, 2,3,7,8-tetrachloridibenzo-p-dioxin; PCBs, polychlorinated biphenyls; PAHs, polycyclic aromatic hydrocarbons; PFOA, perfluorooctanoic acid; DDT, dichlorodiphenyltrichloroethane; DDE, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene; TETs, Ten-Eleven Translocation proteins; DNMTs, DNA methyltransferases; MBDs, methyl-CpG-binding domain proteins; ER, estrogen receptor
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Figure 2
Synergistic effects of in utero exposure to high-fat diet and BPA exposure in increasing mammary tumor incidence in adult life. The dams were fed with high-fat butter (HFB)±BPA (2.5–2500 μg/kg body weight) during acclimation and gestation periods. HFB +25 μg/kg body weight produced the maximal synergistic effects of i) the increased number of terminal end buds (TEBs), estrogen receptor α (ERα), epithelial cell proliferation, and significant loss of 5′hydroxymethylation of cytosine (hmC) and 5′ methylation of cytosine (mC) in the epithelial cells of the TEBs; and ii) increased tumor incidence in the HFB+BPA group when compared with the BPA (or the control-diet AIN).
- © 2014 Society for Endocrinology
