Department of Otolaryngology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Eur J Cancer Prev. 2012 Nov;21(6):569-75. doi: 10.1097/CEJ.0b013e328350b097.
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.
原钙黏蛋白 8(PCDH8)是一种整合膜蛋白,据报道其在癌症中作为肿瘤抑制因子参与肿瘤发生。本研究旨在探讨鼻咽癌(NPC)中 PCDH8 的表观遗传失活及其肿瘤抑制功能。采用半定量 PCR 方法发现 NPC 细胞系中 PCDH8 下调/沉默。甲基化特异性 PCR 显示 PCDH8 的启动子甲基化在 5/5(100%)的细胞系和 35/41(85.3%)的原发肿瘤中存在,但在正常鼻咽组织中不存在。用 5-氮杂-2'-脱氧胞苷和/或曲古抑菌素 A 处理 NPC 细胞可恢复 PCDH8 的表达。在沉默的 NPC 细胞中异位表达 PCDH8 可显著抑制细胞集落形成和细胞迁移。本研究首次证明了 PCDH8 启动子甲基化导致 NPC 中的表观遗传失活及其肿瘤抑制功能。因此,PCDH8 可被鉴定为 NPC 的肿瘤抑制因子。