Department of General Pathology, Dental School, University of São Paulo, São Paulo, Brazil.
Histopathology. 2010 Nov;57(5):689-98. doi: 10.1111/j.1365-2559.2010.03685.x.
Claudins, a large family of essential tight junction (TJ) proteins, are abnormally regulated in human carcinomas, especially claudin-7. The aim of this study was to investigate claudin-7 expression and alterations in oral squamous cell carcinoma (OSCC).
Expression of claudin-7 was analysed in 132 cases of OSCC organized in a tissue microarray. Claudin-7 mRNA transcript was evaluated using real-time polymerase chain reaction and the methylation status of the promoter was also assessed. Claudin-7 was negative in 58.3% of the cases. Loss of claudin-7 protein expression was associated with recurrence (P = 0.019), tumour size (P = 0.014), clinical stage of OSCC (P = 0.055) and disease-free survival (P = 0.015). Down-regulation of the claudin-7 mRNA transcripts was observed in 78% of the cases, in accordance with immunoexpression. Analysis of the methylation status of the promoter region of claudin-7 revealed that treatment of O28 cells (that did not express claudin-7 mRNA transcripts) with 5-Aza-2'-Deoxycytidine (5-Aza-dC) led to the re-expression of claudin-7 mRNA transcript.
Loss of claudin-7 expression is associated with important subcellular processes in OSCC with impact on clinical parameters.
紧密连接(TJ)蛋白家族中的 Claudin 是重要的 TJ 蛋白,在人类癌组织中异常调控,尤其是 Claudin-7。本研究旨在探讨 Claudin-7 在口腔鳞状细胞癌(OSCC)中的表达和改变。
在组织微阵列中分析了 132 例 OSCC 病例中 Claudin-7 的表达。使用实时聚合酶链反应评估 Claudin-7 mRNA 转录本,并且还评估了启动子的甲基化状态。Claudin-7 在 58.3%的病例中呈阴性。Claudin-7 蛋白表达缺失与复发(P = 0.019)、肿瘤大小(P = 0.014)、OSCC 的临床分期(P = 0.055)和无病生存(P = 0.015)相关。在 78%的病例中观察到 Claudin-7 mRNA 转录本的下调,与免疫表达一致。对 Claudin-7 启动子区域的甲基化状态进行分析表明,用 5-氮杂-2'-脱氧胞苷(5-Aza-dC)处理不表达 Claudin-7 mRNA 转录本的 O28 细胞导致 Claudin-7 mRNA 转录本的重新表达。
Claudin-7 表达缺失与 OSCC 中的重要亚细胞过程相关,对临床参数有影响。