Promoter hypomethylation contributes to the expression of MUC3A in cancer cells
Promoter hypomethylation contributes to the expression of MUC3A in cancer cells
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DOI：
10.1016/j.bbrc.2010.05.124
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发表时间：
2010-06-25
影响因子：
3.1
通讯作者：
Yonezawa, Suguru
中科院分区：
文献类型：
--
作者：
Kitamoto, Sho;Yamada, Norishige;Yonezawa, Suguru
MUC 3A是一种膜结合糖蛋白，在癌中异常表达，是预后不良的危险因素。然而，MUC 3A表达的确切机制尚未阐明。在这里，我们提供了第一个证据表明，MUC 3A基因的表达是由近端启动子区域的CpG甲基化状态控制。我们发现DNA甲基化模式与乳腺癌、肺癌、胰腺癌和结肠癌细胞系中MUC 3A的表达密切相关。使用MassARRAY分析绘制了从-660到+273的30个CpG位点的DNA甲基化状态。MUC 3A阴性癌细胞系和具有低MUC 3A表达的那些（例如，MCF-7）在近端启动子区高度甲基化，对应于9个CpG位点（约345至约75 bp），而MUC 3A阳性细胞系（例如，LS 174 T）具有低甲基化水平。此外，5-氮杂-2 '-脱氧胞苷和抑制素A处理MUC 3A阴性细胞或具有低MUC 3A表达的细胞引起MUC 3A mRNA的升高。我们的研究结果表明，DNA低甲基化在MUC 3A基因的5 '-侧翼区发挥了重要作用，MUC 3A在各种器官的癌表达。了解MUC 3A的表观遗传学变化可能有助于癌症患者致癌风险的诊断和预后的预测。(C)2010年爱思唯尔公司All rights reserved.
MUC3A is a membrane-bound glycoprotein that is aberrantly expressed in carcinomas and is a risk factor for a poor prognosis. However, the exact mechanism of MUC3A expression has yet to be clarified. Here, we provide the first evidence that MUC3A gene expression is controlled by the CpG methylation status of the proximal promoter region. We show that the DNA methylation pattern is intimately correlated with MUC3A expression in breast, lung, pancreas and colon cancer cell lines. The DNA methylation status of 30 CpG sites from -660 to +273 was mapped using MassARRAY analysis. MUC3A-negative cancer cell lines and those with low MUC3A expression (e.g., MCF-7) were highly methylated in the proximal promoter region, corresponding to 9 CpG sites (-345 to -75 bp), whereas MUC3A-positive cell lines (e.g., LS174T) had low methylation levels. Moreover, 5-aza-2'-deoxycytidine and trichostatin A treatment of MUC3A-negative cells or those with low MUC3A expression caused elevation of MUC3A mRNA. Our results suggest that DNA hypomethylation in the 5'-flanking region of the MUC3A gene plays an important role in MUC3A expression in carcinomas of various organs. An understanding of epigenetic changes in MUC3A may contribute to the diagnosis of carcinogenic risk and to prediction of outcome in patients with cancer. (C) 2010 Elsevier Inc. All rights reserved.