乳腺癌组织ABCG2基因启动子区甲基化状况与其表达

Methylation status and expression of multidrug resistance gene ABCG2 in breast cancer.

目的研究多药耐药基因ABCG2启动子区甲基化状态与其在乳腺癌组织中表达的关系,探讨ABCG2基因表达的表观遗传学机制。方法采用甲基化特异性PCR(Methylation specific PCR,MSP)检测15例乳腺癌组织及配对癌旁组织中ABCG2启动子区-359～-353两特异位点的甲基化情况,并经MSP产物测序检测位点的甲基化状态;用Q-PCR检测ABCG2基因mRNA的表达水平;并应用统计学Spearman等级相关性方法分析二者的相关关系。结果15例乳腺癌组织中有13例(86.67%)ABCG2基因启动子区的特异位点存在高甲基化(P<0.05),MSP产物的测序验证了特异位点的甲基化,并且mRNA表达水平相对增高,二者之间存在显著正相关性(r2=0.6842,P<0.05)。结论ABCG2基因的启动子区-359～-353位点存在高甲基化,可促进该基因在乳腺癌组织中的表达。

Objective To investigate the methylated status of ABCG2 gene promoter region and expression level of its mRNA, and the epigenetics role of ABCG2 gene in breast cancer. Methods The methylation status of specific CpG sites at -359 - -353 of ABCG2 gene were detected by sensitive MSP assay in carcinous and adjacent normal breast tissue of 15 breast cancer patients and MSP products were used to determine the methylation status of CpG sites in ABCG2 by gene sequence. The expression level of mRNA was detected by Q - PCR. and the correlation of the two was analyzed by spearman rank correlation analysis method. Results There hypermethylation was observed in specific sites of ABCG2 gene promoter region of 13 cases （ 13/15, 86.67% ） and gene sequence validate it and the expression level of mRNA was relatively increased, showing significant psotive correaltion （ r = 0. 6842, P 〈 0.05 ）. Conclusion There are hypermethylatian in sites of - 359 - - 353 of ABCG2 gene in breast cancer patients and , which may contributes to its expression in breast cancer.