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Methylation of Notch3 modulates chemoresistance via P-glycoprotein

Research paper by Xiaoting Gu, Yangfan Lu, Dongxu He, Chunxiao Lu, Jian Jin, Xiaojie Lu, Xin Ma

Indexed on: 22 Oct '16Published on: 22 Oct '16Published in: European Journal of Pharmacology



Abstract

The global gene expression and DNA methylation of genes in adriamycin-resistant human breast cancer cells (MCF-7/ADM cells) are similar to those in paclitaxel-resistant MCF-7 cells (MCF-7/PTX) and are significantly different from those in wild-type MCF-7 cells. DNA methylation is associated with chemoresistance in breast cancer and changes the characteristics of chemoresistant and chemosensitive cells. Here, we showed that the tumor-suppressor gene Notch3 was inactivated due to epigenetic silencing DNA hypermethylation in MCF-7/ADM cells. In addition, the drug efflux pump P-glycoprotein was negatively regulated by Notch3 and highly expressed in MCF-7/ADM cells. Taken together, our findings demonstrated that hypermethylation of Notch3 causes activation of P-glycoprotein in adriamycin-resistant cells.

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