Breast cancer can be driven by several different epigenetic mechanisms. Histone methylation by the Ezh2 protein drives gene silencing required for the maintenance of cell identity. Dysregulation of histone methylation leads to loss of cell identity, which in turn leads to neoplastic transformation and increased breast tumor invasiveness. Additionally, transcriptional repression due to the hypermethylation of nuclear receptor promoter regions leads to the formation of ER– and/or PR– breast cancers that are not responsive to tamoxifen. Finally, phosphorylation of ER at Ser167 promotes ER-dependent transcription and is attributed to increased resistance to tamoxifen
Overexpression of Ezh2 plays a role in many cancers, including breast cancer, where it adds methyl groups to H3K27 triggering gene silencing.
UTX is a counterpart to Ezh2 that removes methyl groups from H3K27.
Mutations in nuclear receptors such as Estrogen Receptor α and Progesterone Receptor will alter gene expression and can have a huge impact on treatment options in breast cancer.