CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma
CDH4 as a novel putative tumor suppressor gene epigenetically silenced by promoter hypermethylation in nasopharyngeal carcinoma
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CDH4作为一种新型推定肿瘤抑制基因，在鼻咽癌中通过启动子高甲基化而被表观遗传沉默
DOI：
10.1016/j.canlet.2011.05.016
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发表时间：
2011-10-01
期刊：
影响因子：
9.7
通讯作者：
Zhang, Zhe
中科院分区：
文献类型：
--
作者：
Du, Chunping;Huang, Tingting;Zhang, Zhe
我们研究了鼻咽癌组织中钙粘蛋白CDH4的转录水平、启动子甲基化状态及其作为肿瘤抑制基因(TSG)的作用。CDH4在鼻咽癌细胞系、异种移植瘤和原发肿瘤活检组织中的表达降低。CDH4启动子高甲基化在5个鼻咽癌细胞系、鼻咽癌移植瘤系和94.3%的原发肿瘤中均可检测到，但在12例正常鼻咽癌组织中均未检测到。甲基转移酶抑制剂5-氮-2‘-脱氧胞苷可恢复鼻咽癌细胞CDH4的表达。CDH4在鼻咽癌细胞系中的异位表达抑制了细胞的增殖、集落形成、迁移和诱导细胞通讯。CDH4可能是一种新的TSG，在鼻咽癌中可以被其启动子甲基化频繁地和肿瘤特异性失活。(C)2011爱思唯尔爱尔兰有限公司。保留所有权利。
We investigated the transcription levels, promoter methylation status and role as a tumor suppressor gene (TSG) of the cadherin CDH4 in nasopharyngeal carcinoma (NPC). The expression of CDH4 was decreased in NPC cell lines, xenografts and primary tumor biopsies. Promoter hypermethylation of CDH4 was detected in all five NPC cell lines, both NPC xenograft lines and 94.3% of primary tumors but not in any of the 12 normal epithelial samples. Loss of CDH4 expression could be restored by the methyltransferase inhibitor 5-aza-2'-deoxycytidine in NPC cell lines. Ectopic expression of CDH4 in the NPC cell lines inhibits cell proliferation, colony formation, migration and elicit cell communication. CDH4 may be a novel putative TSG that can be frequently and tumor-specifically inactivated by its promoter methylation in NPC. (C) 2011 Elsevier Ireland Ltd. All rights reserved.