Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer
Variable promoter region CpG island methylation of the putative tumor suppressor gene Connexin 26 in breast cancer
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DOI：
10.1093/carcin/23.2.231
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发表时间：
2002-02-01
期刊：
影响因子：
4.7
通讯作者：
Dobrovic, A
中科院分区：
文献类型：
--
作者：
Tan, LW;Bianco, T;Dobrovic, A
通过间隙连接的细胞间通讯是抑制肿瘤的一种机制。连接蛋白26 （Connexin 26, Cx26）是乳腺上皮细胞表达的间隙连接的结构成分。在许多乳腺肿瘤中，Cx26的表达水平降低。甲基化敏感单链构象分析显示，20名乳腺癌患者中有11名（55%）的启动子区域CpG岛甲基化变化。甲基化模式在肿瘤之间和肿瘤内部均存在异质性。甲基化程度从几个CpG二核苷酸到几乎所有分析区域的CpG二核苷酸不等。最常甲基化的CpG位于Sp1位点，已知该位点对Cx26基因表达很重要。8个乳腺癌细胞系中有一个（MD-MBA-453）在启动子区域甲基化，不表达Cx26。用5-aza-2'-脱氧胞苷处理MDA-MB-453可导致Cx26 mRNA的重新表达。启动子区域的甲基化可能是调节乳腺癌中Cx26表达的重要机制。
Intercellular communication via gap junctions is a mechanism for tumor suppression. Connexin 26 (Cx26) is a structural component of gap junctions expressed by breast epithelial cells. Expression levels of Cx26 are reduced in many breast tumors. Methylation-sensitive single-stranded conformation analysis showed variable methylation in the promoter region CpG island in 11 out of 20 (55%) breast cancer patients. Heterogeneity in methylation patterns was observed both between and within tumors. The degree of methylation ranged from a few CpG dinucleotides to almost all the CpG dinucleotides in the analyzed region. The most frequently methylated CpG was in an Sp1 site known to be important for Cx26 gene expression. One of eight breast cancer cell lines (MD-MBA-453) was methylated in the promoter region and did not express Cx26. Treatment of MDA-MB-453 with 5-aza-2'-deoxycytidine resulted in the re-expression of Cx26 mRNA. Methylation of the promoter region is likely to be an important mechanism in modulating the expression of Cx26 in breast cancer.