title: Methylation of Notch3 modulates chemoresistance via P-glycoprotein.
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.
authors: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors: Xiaoting
authors: X
authors: Gu
authors: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors: Yangfan
authors: Y
authors: Lu
authors: National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors: Dongxu
authors: D
authors: He
authors: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors: Chunxiao
authors: C
authors: Lu
authors: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors: Jian
authors: J
authors: Jin
authors: Wuxi Neuroscience Center of Jiangnan University & Department of Neurosurgery, Wuxi Second Hospital Affiliated Nanjiang Medical University & Wuxi Second People's Hospital, Jiangsu Province, China. Electronic address: xiaojieluwuxi@163.com.
authors: Xiaojie
authors: X
authors: Lu
authors: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China. Electronic address: maxin@jiangnan.edu.cn.
authors: Xin
authors: X
authors: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000494:pharmacology; D000071656:Receptor, Notch3 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071656:Receptor, Notch3; D004317:Doxorubicin; D017239:Paclitaxel
keywords: Breast cancer; Chemoresistance; DNA methylation; Notch3; P-glycoprotein