Park Hannah Lui, Kim Myoung Sook, Yamashita Keishi, Westra William, Carvalho Andre Lopes, Lee Juna, Jiang Wei-Wen, Baek Jin Hyen, Liu Junwei, Osada Motonobu, Moon Chul-So, Califano Joseph A, Mori Masaki, Sidransky David
Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Int J Cancer. 2008 Jun 1;122(11):2498-502. doi: 10.1002/ijc.23434.
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.
结直肠癌缺失基因（DCC）是一种假定的肿瘤抑制基因，其缺失与结直肠癌的发生有关。在包括食管癌在内的多种人类癌症中，均已证实DCC表达降低或缺失。在本研究中，我们通过亚硫酸氢盐测序、甲基化特异性PCR（MSP）和/或定量甲基化特异性PCR（qMSP）分析了食管鳞状细胞癌（ESCC）细胞系、原发性ESCC以及正常食管组织中的DCC甲基化情况。当qMSP阳性的临界值设定为1.0时，在12个检测的ESCC细胞系中的10个、74%的原发性ESCC（n = 70）、0%的相应正常食管组织（n = 20）以及0%的健康个体的正常食管（n = 19）中检测到DCC甲基化。在大多数ESCC细胞系中未检测到DCC表达，而用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过表达抑制了ESCC细胞系中的集落形成，提示DCC可能在食管中作为肿瘤抑制基因发挥作用。然而，DCC甲基化与所测量的任何临床或病理参数均无关联。我们已经证明，DCC甲基化在原发性ESCC中是一种常见且癌症特异性的事件，提示DCC及相关通路可能代表一个新的诊断治疗靶点。
