Title Methylation of matrix metalloproteinases-2 promoter in endometrial cancer invasion
Authors Hu Qian
Yu Li
Liao Qin-ping
Affiliation Department of Gynecology and Obstetrics, Peking University First Hospital, Beijing, China.
Issue Date 2012
Publisher 开云app体育 学报 医学版
Citation Beijing da xue xue bao. Yi xue ban.2012,44,(6),911-5.
Abstract To investigate the regulation of DNA methylation on the expression of MMP-2 gene, and the effect of 5-aza-2'-deoxycytidine (5-aza-CdR) on invasiveness of endometrial cancer cells.Human endometrial cancer cell lines Ishikawa and HEC-1A were treated with 5-aza-CdR. After genomic DNA was extracted from the cells and treated with bisulfate sodium, clone sequencing was used to detect methylation of the matrix metalloproteinases-2 (MMP-2) promoter region. Ishikawa and HEC-1A cells were treated with different concentrations of 5-aza-CdR, and the effect on the invasion and metastasis to the endometrial cancer (EC) cells were detected by Transwell invasion chamber. The MMP-2 mRNA expression was detected by real-time quantitative PCR.Although the MMP-2 promoter showed global hypomethylation status, the methylation of CG dinucleotide sites located on the transcription factor binding sites had high positive frequencies, which were 80% and 70% in HEC-1A cells and 60% and 40% in Ishikawa cells, respectively. The methylation frequencies reduced to 20% and 10% in HEC-1A cells by demethylating agent 5-aza-CdR and the CG sites in Ishikawa cells were totally demethylated. Moreover, after 72 h of treatment with different concentrations of 5-aza-CdR, the expression of the MMP-2 mRNA and transmembrane number of both Ishikawa and HEC-1A cells were significantly upregulated compared with the control group (P<0.05).Methylation of CG dinucleotide sites of the MMP-2 promotor region may be associated with the regulation of gene transcription. The 5-aza-CdR can promote the invasion and metastasis of endometrial cancer cells in vitro by upregulating the MMP-2 mRNA expression.
URI http://hdl.handle.net/20.500.11897/304237
ISSN 1671-167X
Indexed PubMed
Appears in Collections: 第一医院

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