DCC promoter hypermethylation in esophageal squamous cell carcinoma
DCC promoter hypermethylation in esophageal squamous cell carcinoma
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DOI：
10.1002/ijc.23434
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发表时间：
2008-06-01
影响因子：
6.4
通讯作者：
Sidransky, David
中科院分区：
文献类型：
--
作者：
Park, Hannah Lui;Kim, Myoung Sook;Sidransky, David
大肠癌基因（DCC）是一种公认的抑癌基因，其缺失与大肠癌的发生有关. DCC表达的降低或丧失已经在许多人类癌症中得到证实，包括食管癌。在这项研究中，我们分析了食管鳞状细胞癌（ESCC）细胞系和原发性ESCC以及正常食管组织DCC甲基化亚硫酸氢盐测序，甲基化特异性PCR（MSP）和/或定量甲基化特异性PCR（qMSP）。当阳性的qMSP截止值设定为1.0时，在12个测试的ESCC细胞系中的10个中检测到DCC甲基化。74%的原发性ESCC（n = 70），0%的相应正常食管组织（n = 20）和0%的健康个体的正常食管（n = 19）。DCC表达在大多数ESCC细胞系中检测不到，用DNA甲基转移酶抑制剂5-氮杂-2 '-脱氧胞苷处理可重新激活基因表达。DCC过表达抑制ESCC细胞系的集落形成，表明DCC可能在食管中起肿瘤抑制基因的作用。然而，DCC甲基化与测量的任何临床或病理参数无关。我们已经证明DCC甲基化是原发性ESCC中常见的癌症特异性事件，这表明DCC及其相关通路可能代表新的诊断治疗靶点。(C)2008 Wiley-Liss，Inc.
Deleted in Colorectal Cancer (DCC) is a putative tumor suppressor gene, whose loss has been implicated in colorectal tumorigenesis. Decreased or loss of DCC expression has been demonstrated in a number of human cancers, including esophageal cancer. In this study, we analyzed esophageal squamous cell carcinoma (ESCC) cell lines and primary ESCCs as well as normal esophageal tissues for DCC methylation by bisulfite sequencing, methylation-specific PCR (MSP) and/or quantitative methylation-specific PCR (qMSP). When a qMSP cut-off value for positivity was set to 1.0, DCC methylation was detected in 10 of 12 ESCC cell lines tested., 74% of primary ESCCs (n = 70), 0% of corresponding normal esophageal tissues (n = 20) and 0% of normal esophagus from healthy individuals (n = 19). DCC expression was undetectable in the majority of ESCC cell lines, and treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine reactivated gene expression. DCC overexpression suppressed colony formation in ESCC cell lines, suggesting that DCC may function as a tumor suppressor gene in the esophagus. However, DCC methylation was not associated with any clinical or pathologic parameters measured. We have demonstrated that DCC methylation is a frequent and cancer-specific event in primary ESCCs, suggesting that DCC and associated pathways may represent a new diagnostical therapeutic target. (C) 2008 Wiley-Liss, Inc.