Nuclear receptors and epigenetic regulation

The activity of nuclear receptor (NR) at target genes is regulated by the interaction with ligands, coactivators, corepressors, DNA, and histone-modifying proteins. These interactions influence chromatin status and transcription of genes encoding for factors that impinge on breast cancer processes such as cell proliferation, invasion and metastasis, DNA repair, and differentiation. Epigenetic mechanisms such as DNA methylation at CpG islands and histone modifications influence transcriptional activity directed by various NR including the estrogen, progesterone, aromatic hydrocarbon, vitamin D, and retinoic X receptor. In breast tissues, dietary compounds may alter cancer risk through agonistic and antagonistic interactions toward one or more NR. Examples of food ligands for NR include resveratrol, genistein, curcumin, vitamin D, and omega-3 fatty acids. Based on the information that ~80% of breast cancer cases are sporadic, i.e., lack a hereditary origin, studies that focus on the interaction of specific or combinations of food compounds with NR promise to unravel new epigenetic strategies against breast cancer.