Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma
Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma
复制标题
DOI：
10.1097/cej.0b013e328350b097
复制
发表时间：
2012-11-01
影响因子：
2.4
通讯作者：
Hu, Guohua
中科院分区：
文献类型：
--
作者：
He, Dan;Zeng, Quan;Hu, Guohua
原钙粘蛋白 8 (PCDH8) 是一种整合膜蛋白，据报道是参与癌症肿瘤发生的肿瘤抑制因子。我们的目的是研究 PCDH8 的表观遗传失活及其在鼻咽癌 (NPC) 中的抑癌功能。使用半定量 PCR 发现 NPC 细胞系中 PCDH8 频繁下调/沉默。通过甲基化特异性 PCR，在 100% (5/5) 的细胞系和 85.3% (35/41) 的原发性肿瘤中观察到 PCDH8 启动子甲基化，但在正常鼻咽组织中未观察到。用 5-aza-2'-deoxycytidine 和/或曲古抑菌素 A 处理 NPC 细胞可以恢复 PCDH8 表达。沉默的NPC细胞中PCDH8的异位表达显着抑制细胞集落形成和细胞迁移。我们的研究首次证明了 PCDH8 通过启动子甲基化的表观遗传失活及其在鼻咽癌中的肿瘤抑制功能。因此，PCDH8 可以被鉴定为 NPC 中的肿瘤抑制因子。欧洲癌症预防杂志 21：569-575 (C) 2012 Wolters Kluwer Health 垂直条 Lippincott Williams & Wilkins。
Protocadherin8 (PCDH8), an integral membrane protein, was reported to be a tumor suppressor involved in tumorigenesis in cancers. We aimed to investigate the epigenetic inactivation of PCDH8 and its tumor-suppressor function in nasopharyngeal carcinoma (NPC). Frequent downregulation/silencing of PCDH8 was found in NPC cell lines using semiquantitative PCR. Promoter methylation of PCDH8 was observed in 100% (5/5) of cell lines and 85.3% (35/41) of primary tumors by methylation-specific PCR, but not in normal nasopharyngeal tissues. Treatment of NPC cells with 5-aza-2'-deoxycytidine and/or trichostatin A could restore PCDH8 expression. Ectopic expression of PCDH8 in silenced NPC cells significantly inhibited cell colony formation and cell migration. For the first time, our study demonstrates the epigenetic inactivation of PCDH8 by promoter methylation and its tumor-suppressive function in NPC. Thus, PCDH8 could be identified as a tumor suppressor in NPC. European Journal of Cancer Prevention 21: 569-575 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.