BRCA1 and Estrogen Receptor α Expression Regulation in Breast Cancer Cells

Scherbakov, A.M.; Shestakova, E.A.; Galeeva, K.E.; Bogush, T.A.

Авторы: Scherbakov A.M., Shestakova E.A., Galeeva K.E., Bogush T.A.
Журнал: Molecular Biology
Том: 53
Номер: 3
Год издания: 2019
Издательство: Maik Nauka/Interperiodica Publishing
Местоположение издательства: Russian Federation
Первая страница: 442
Последняя страница: 451
DOI: 10.1134/s0026893319030166
Аннотация: Abstract—BRCA1 (breast cancer 1) protein is involved in the genome stability maintenance participating inhomologous recombination-dependent DNA repair. Disruption of BRCA1 functioning is associated withbreast and ovarian cancer. Despite the important role of BRCA1 in DNA repair in all cell types, the developmentof BRCA1-associated cancer takes place mainly in estrogen-dependent tissues such as breast and ovarianones. Using breast cancer cell line MCF-7 it was demonstrated in in vitro experiments that the estrogen17β-estradiol (E2), phytoestrogens (genistein and apigenin) and antiestrogens (tamoxifen and fulvestrant)inhibited estrogen receptor α (ERα) expression while only genistein influenced BRCA1 increasing its expression.In hypoxia, that is an important factor of solid tumors progression, the decrease of BRCA1 and ERαexpression was demonstrated in MCF-7 cells. Therefore, hypoxia influences both BRCA1-dependent DNArepair and hormonal regulation of breast cancer cell growth. Taken together, obtained results demonstrate arelationship between BRCA1 and steroid hormones signal transduction pathways in breast cancer cells andpoint out to the importance of complex BRCA1 and ERα expression regulation mechanisms studies includingepigenetic gene expression regulation.Keywords: BRCA1 protein, estrogen receptors, breast cancer, MCF-7, flow cytometry, hypoxia, phytoestrogens,estrogens
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