A Review on EZH2 and its Epigenetic Association with Breast Cancer

Abstract

Enhancer of zeste homolog2 (EZH2), first identified as homolog of the Drosophila enhancer of zeste gene, is histone H3 lysine methyltransferase (H3K27me3), a component of polycomb group proteins (PRC2) that represses the gene expression by modifying the histones epigenetically, thereby silencing developmental regulatory elements in stem as well as cancer cells leading to repression of early differentiation marker genes. Although the mechanistic approach of involving EZH2 to cancer progression has not yet been clearly deciphered, its invasiveness and metastatic potential has been revealed by significant elevation of its expression in normal breast cancer cells after commencement of which a pre-cancerous state was found in morphologically normal breast cancer cells. The tissue microarray analysis of breast carcinomas has shown that EZH2 to be intimately associated with markers of tumor cell proliferation as well as with aggressive diseases. Till now, no demethylating agents have been recommended for treatment of patients, but an in-vitro study using 3-deazaneplanocin, which reduces histone modifications through methylation by reducing the levels of EZH2, has shown a significant reduction in cell proliferation in breast cancer cells. This further signifies the role of EZH2 as a transcriptional repressor. By analyzing methylation profiles of different subtypes of breast cancers like basal-like, luminal A & B, roles of EZH2 have been established in the development of breast cancers. Crosstalk of EZH2 with other silencing/regulating factors like histone deacetylases and miRNAs, have to be considered for evaluating for progression of cell proliferation in different cancer cells including breast cancer.