The effect of DNA methyltransferase 3A suppression in progression of the resistance phenotype in breast cancer cellsстатьяКраткое сообщение
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Дата последнего поиска статьи во внешних источниках: 15 февраля 2024 г.
Аннотация:Introduction. Rearrangement of molecular pathways and activation of bypass signaling determine the progressionof tumor cell resistance to various drugs. Study of the common features of resistant formation mechanisms is essentialfor breast and other cancer beneficial treatments.Materials and methods. The present work was performed on estrogen receptor α ERα-positive (ERα – estrogen receptor α)McF-7 breast cancer cells, established sublines resistant to the mTOR inhibitor rapamycin or antiestrogen tamoxifen, andERα-negative MDA-MB-231 breast cancer cells. Methods used include MTT test, transient transfection, immunoblotting,real-time polymerase chain reaction and methylation analysis by bisulfite pyrosequencing.Results. We have shown that the resistance of breast cancer cells to targeted and hormonal drugs is associated with thesuppression of DNA methyltransferase 3A (DNMT3A) and respective changes in DNA methylation; DNMT3A knockdownresults in the partial resistance to both drugs demonstrating the pivotal role of DNMT3A suppression in the progressionof cell resistance.Conclusion. Totally, the results obtained highlight the possible mechanism of tumor cell resistance to targeting/hormonal drugs based on the deregulation of DNMTs expression and demonstrate direct connection between DNMT3Asuppression and resistance progression.Keywords: rapamycin, tamoxifen, drug resistance, McF-7 cells, protein kinase AKT, DNA methyltransferase, LINE repeats