Downregulation of EphA7 by hypermethylation in colorectal cancer
Downregulation of EphA7 by hypermethylation in colorectal cancer
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DOI：
10.1038/sj.onc.1208720
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发表时间：
2005-08-25
期刊：
影响因子：
8
通讯作者：
Sugimura, H
中科院分区：
文献类型：
--
作者：
Wang, JD;Kataoka, H;Sugimura, H
与相应的正常粘膜（P = 0.008）和五种结肠癌细胞系相比，对 59 个结直肠癌组织进行半定量逆转录聚合酶链式反应分析，显示人类结直肠癌中 EphA7 表达显着降低。为了研究结直肠癌中 EphA7 下调的机制，我们使用限制性内切酶、甲基化特异性 PCR 和亚硫酸氢盐测序检查了五个结肠癌细胞系中翻译起始位点周围 5'CpG 岛的甲基化状态，并发现了异常甲基化的证据。结肠癌细胞系中 EphA7 的表达在用 5-aza-2'-deoxycytidine 处理后恢复。对75个肿瘤的甲基化状态与临床病理参数进行比较分析发现，结直肠癌的高甲基化在男性中比在女性中更常见（P=0.0078），在中分化腺癌中比在高分化腺癌中更常见（P=0.0361）。直肠癌中高甲基化的发生率高于结肠癌（P=0.0816）。在结直肠腺瘤中也观察到高甲基化。这是第一份描述实体瘤中 Eph 家族基因通过异常 5'CpG 岛甲基化下调的报告。为EphA7基因参与人类结直肠癌发生提供了证据。
A significant reduction of EphA7 expression in human colorectal cancers was shown using semiquantitative reverse transcription-polymerase chain reaction analysis in 59 colorectal cancer tissues, compared to corresponding normal mucosas (P=0.008), and five colon cancer cell lines. To investigate the mechanism of EphA7 down-regulation in colorectal cancer, we examined the methylation status of the 5'CpG island around the translation start site in five colon cancer cell lines using restriction enzymes, methylation-specific PCR, and bisulfite sequencing and found evidence of aberrant methylation. The expression of EphA7 in colon cancer cell lines was restored after treatment with 5-aza-2'-deoxycytidine. Analysis of methylation status in totally 75 tumors compared to clinicopathological parameters revealed that hypermethylation of colorectal cancers was more frequent in male than in female (P=0.0078), and in moderately differentiated than in well-differentiated adenocarcinomas (P=0.0361). There was a tendency that hypermethylation in rectal cancers was more frequent than in colon cancers (P=0.0816). Hypermethylation was also observed in colorectal adenomas. This is the first report describing the downregulation of an Eph family gene in a solid tumor via aberrant 5'CpG island methylation. It provides the evidence that EphA7 gene is involved in human colorectal carcinogenesis.