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Epigenetic regulation of BRCA1 expression and its role in breast cancer stem cell development

The tumor suppressor breast cancer 1, early onset (BRCA1) plays an important role in maintaining the genome integrity, actively participating in DNA repair via homologous recombination. The level of functional final BRCA1 protein is precisely regulated in cells. | Turkish Journal of Biology http://journals.tubitak.gov.tr/biology/ Review Article Turk J Biol (2016) 40: 981-989 © TÜBİTAK doi:10.3906/biy-1507-145 Epigenetic regulation of BRCA1 expression and its role in breast cancer stem cell development Elena A. SHESTAKOVA* Laboratory of Medical Chemistry, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation Received: 31.07.2015 Accepted/Published Online: 25.01.2016 Final Version: 08.11.2016 Abstract: The tumor suppressor breast cancer 1, early onset (BRCA1) plays an important role in maintaining the genome integrity, actively participating in DNA repair via homologous recombination. The level of functional final BRCA1 protein is precisely regulated in cells. Epigenetic regulation of BRCA1 gene expression is one of the most important mechanisms for BRCA1 level fine-tuning. In this review the main epigenetic mechanisms of BRCA1 expression regulation are presented, including DNA methylation, histone covalent modifications, and regulation with transcription factors. Another important function of BRCA1 emerging in recent years is its role in the regulation of breast cancer stem cell development. Moreover, based on its multiple functions, BRCA1 is also arising as a powerful biomarker. In particular, it could be used as a prognostic marker of the course of the disease and as a predictive marker of the efficiency of platinum-based chemotherapy. Key words: Breast cancer 1, early onset, (BRCA1) epigenetic regulation, histone, DNA modifications, breast cancer stem cells 1. Introduction Breast cancer 1, early onset (BRCA1) is a tumor suppressor. The BRCA1 protein has a molecular weight of 220 kDa (Clark et al., 2012) and is coded with the 85-kb BRCA1 gene located on chromosome 17q (Barker et al., 1996; Tan-Wong et al., 2008). Mutations in the BRCA1 gene induce the early onset of hereditary forms of breast cancer (BC) and ovarian cancer (OC). At the molecular level mutations in the BRCA1 gene lead to the .