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• W2590203437 startingPage "101042831769225" @default.
• W2590203437 abstract "Arsenic trioxide (As 2 O 3 ) has been used clinically as an anti-tumor agent. Its mechanisms are mostly considered to be the induction of apoptosis and cell cycle arrest. However, the detailed molecular mechanisms of its anti-cancer action through cell cycle arrest are poorly known. Furthermore, As 2 O 3 has been shown to be a potential DNA methylation inhibitor, inducing DNA hypomethylation. We hypothesize that As 2 O 3 may affect the expression of cell cycle regulatory genes by interfering with DNA methylation patterns. To explore this, we examined promoter methylation status of 24 cell cycle genes in breast cancer cell lines and in a normal breast tissue sample by methylation-specific polymerase chain reaction and/or restriction enzyme–based methods. Gene expression level and cell cycle distribution were quantified by real-time polymerase chain reaction and flow cytometric analyses, respectively. Our methylation analysis indicates that only promoters of RBL1 (p107), RASSF1A, and cyclin D2 were aberrantly methylated in studied breast cancer cell lines. As 2 O 3 induced CpG island demethylation in promoter regions of these genes and restores their expression correlated with DNA methyltransferase inhibition. As 2 O 3 also induced alterations in messenger RNA expression of several cell cycle–related genes independent of demethylation. Flow cytometric analysis revealed that the cell cycle arrest induced by As 2 O 3 varied depending on cell lines, MCF-7 at G1 phase and both MDA-MB-231 and MDA-MB-468 cells at G2/M phase. These changes at transcriptional level of the cell cycle genes by the molecular mechanisms dependent and independent of demethylation are likely to represent the mechanisms of cell cycle redistribution in breast cancer cells, in response to As 2 O 3 treatment." @default.
• W2590203437 created "2017-03-03" @default.
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• W2590203437 date "2017-02-01" @default.
• W2590203437 modified "2023-09-23" @default.
• W2590203437 title "Demethylation and alterations in the expression level of the cell cycle–related genes as possible mechanisms in arsenic trioxide–induced cell cycle arrest in human breast cancer cells" @default.
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• W2590203437 doi "https://doi.org/10.1177/1010428317692255" @default.
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• W2590203437 hasPublicationYear "2017" @default.
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