title: ERα positively regulated DNMT1 expression by binding to the gene promoter region in human breast cancer MCF-7 cells.
abstract: Estrogen receptors (ER) are expressed in approximately 65% of human breast cancer. Clinical trials and retrospective analyses showed that ER-positive (ER+) tumors were more vulnerable to development of chemotherapy resistance than ER-negative (ER-) tumors. The underlying mechanism is still to be elucidated. Aberrant DNA methylation has been recognized to be associated with cancer chemotherapy resistance. Recently, steroid hormone and their receptors have been found to be involved in the regulation of methyltransferases (DNMTs) and thereby contribute to chemotherapy resistance. The purpose of this study is to explore whether ERα could directly regulate the DNMTs expression. We first analyzed the methylation alterations and its correlation with the expression levels of three types of DNMTs in our established paclitaxel-resistant breast cancer lines, MCF-7(ER+)/PTX and MDA-MB-231(ER-)/PTX cell lines, using qMSP, real-time PCR and Western blot. Then we determined the function of ERα in regulation of DNMT1 using luciferase report gene systems. Our data demonstrated for the first time that ERα could upregulate DNMT1 expression by directly binding to the DNMT1 promoter region in MFC-7(ER+)/PTX cells.
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, China. njm_x.student@sina.com
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Shi
authors.forename: Xing-Jia
authors.initials: XJ
authors.lastname: Li
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Si
authors.forename: An-Di
authors.initials: AD
authors.lastname: Li
authors.forename: Hai-Jian
authors.initials: HJ
authors.lastname: Ding
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Sun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004790:Enzyme Induction; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D017239:Paclitaxel