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Феномен подавления эстрогенового сигналинга в клетках рака молочной железы под действием ультрафиолетового облучения: роль белков Snailстатья Исследовательская статья
Статья опубликована в журнале из списка Web of Science и/или Scopus
- Авторы: Сорокин Д.В., Андреева О.Е., Щербаков А.М., Сальникова Д.И., Гудкова М.В., Красильников М.А.
- Журнал: Успехи молекулярной онкологии
- Том: 10
- Номер: 4
- Год издания: 2023
- Издательство: АБВ-пресс
- Местоположение издательства: М.
- Первая страница: 108
- Последняя страница: 115
- DOI: 10.17650/2313-805X-2023-10-4-108-115
- Аннотация: Introduction. The study of the effect of irradiation or any other DNA-damaging agents on the sensitivity of tumors to conservative therapy, drug or hormonal, is among the most imporant tasks that determine the efficiency of combined therapy of cancer patients.Aim. To investigate the effect of irradiation on the activity of key signaling proteins and the level of hormone dependence of breast cancer cells.Materials and methods. The experiments were performed on in vitro cultured estrogen-dependent McF-7 breast cancer cells. ultraviolet (uV) irradiation in the range of 254 nm with the intensity of 25–50 J/m2 was used as an experimentalmodel to study the response of tumor cells to DNA damage. cell growth rate was determined using the MTT test, cell survival after irradiation was analyzed using the colony-forming test. Estrogen receptor transcriptional activity was determined by reporter assay; cellular protein expression was determined by immunoblotting.Results. Single uV irradiation of McF-7 cells leads to a marked increase in the level of apoptotic markers: p53, cPARP, suppression of expression of growth signaling proteins: cDK4/6 and estrogen receptor α (ERα). The above changes areaccompanied with an increase in phosphorylation of Akt protein kinase and a marked increase in the expression of Snail1, one of the key proteins of epithelial-mesenchymal transition. In uV-resistant McF-7/uVR cell subline obtained under repeated irradiation cycles, the levels of apoptotic and growth signaling proteins (p53, cPARP, cDK4/6) return to controllevels, except for the phosphorylated form of Akt and Snail1, whose content remains high. Transfection of Snail1-expressing plasmid into McF-7 cells is accompanied by activation of apoptotic signaling, suppression of ERα activity, anddevelopment of partial hormone resistance; however, the sensitivity of cells to irradiation is practically unchanged.Transfection of microRNA-181a-2, one of the microRNAs associated with cell resistance, simultaneously activates Aktand Snail1 and leads to the development of cross-resistance of cells to irradiation and hormonal drugs.Conclusion. The obtained data allow us to consider irradiation-induced Snail1 activation as one of the factors involvedin deregulation of estrogen signaling and formation of cell resistance to hormonal drugs, while simultaneous activationof Akt and Snail1 is accompanied by the development of cross-resistance to irradiation and hormonal drugs.Keywords: breast cancer, hormonal resistance, irradiation, estrogen receptor, Snail1, protein kinase Akt
- Добавил в систему: Сальникова Диана Игоревна