Quantitative hypermethylation of NMDAR2B in human gastric cancer
Quantitative hypermethylation of NMDAR2B in human gastric cancer
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DOI：
10.1002/ijc.22934
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发表时间：
2007-11-01
影响因子：
6.4
通讯作者：
Sidransky, David
中科院分区：
文献类型：
--
作者：
Liu, Jun-Wei;Kim, Myoung Sook;Sidransky, David
NMDA受体2B型（NMDAR2B）是首次在食管鳞状细胞癌（ESCC）中发现的候选TSG。为了评估NMDAR2B甲基化在胃癌进展中的作用，我们在胃原代组织中进行了定量甲基化特异性PCR （MSP）、RTPCR和免疫组织化学（IHC），并在胃癌细胞系中进行了集落形成实验。我们发现NMDAR2B的表达被去甲基化剂5-aza-2'-脱氧胞苷在加或不加曲古霉素A的情况下在胃癌细胞系中重新激活。此外，NMDAR2B的失活被发现与胃细胞系和原发性胃肿瘤的启动子甲基化状态密切相关。免疫组化数据还显示，NMDAR2B在胃上皮细胞中特异性表达，在胃癌上皮中表达减少或缺失。定量分析NMDAR2B启动子甲基化显示，原发性胃肿瘤中有61%（17/28）的超甲基化，而非胃癌患者正常胃组织中有5%（1/20）的超甲基化。NMDAR2B在胃癌细胞系中强制过表达可显著抑制细胞集落形成。综上所述，上述结果表明NMDAR2B甲基化是胃癌进展中常见且重要的生物学相关事件。(c) 2007 Wiley-Liss, Inc。
NMDA receptor Type 2B (NMDAR2B) is a candidate TSG first identified in esophageal squamous cell carcinoma (ESCC). To evaluate NMDAR2B methylation in gastric cancer progression, we performed quantitative methylation-specific PCR (MSP), RTPCR and immnunohistochemistry (IHC) in primary gastric tissues and colony formation assays in gastric cancer cell lines. We found that the expression of NMDAR2B was reactivated by the demethylating agent, 5-aza-2'-deoxycytidine, with or without trichostatin A in gastric cancer cell lines. Moreover, inactivation of NMDAR2B was found to be closely correlated with promoter methylation status in gastric cell lines-and primary gastric tumors. IHC data also showed that NMDAR2B was specifically expressed in gastric epithelial cells and its expression was diminished or absent in gastric cancer epithelium. Quantitative analysis of NMDAR2B promoter methylation showed 61% (17/28) hyper-methylation in primary gastric tumors versus 5% (1/20) in normal gastric tissues from nongastric cancer patients. Forced overexpression of NMDAR2B in gastric cancer cell lines significantly inhibited cell colony formation. Taken together, the above results suggest that NMDAR2B methylation is a common and important biologically relevant event in gastric cancer progression. (c) 2007 Wiley-Liss, Inc.