Quantitative hypermethylation of NMDAR2B in human gastric cancer.

Abstract

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), RT-PCR 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) hypermethylation in primary gastric tumors versus 5% (1/20) in normal gastric tissues from nongastric cancer patients. Forced over-expression 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.

• Authors: Jun-Wei Liu, Myoung Sook Kim, Jatin Nagpal, Keishi Yamashita, Luana Poeta, Xiaofei Chang, Juna Lee, Hannah Lui Park, Carmen Jeronimo, William H Westra, Masaki Mori, Chulso Moon, Barry Trink, David Sidransky
• Journal: International journal of cancer (Int J Cancer) Vol. 121 Issue 9 Pg. 1994-2000 (Nov 01 2007) ISSN: 0020-7136 [Print] United States
• PMID: 17620329 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2007 Wiley-Liss, Inc.

Chemical References

• Biomarkers, Tumor
• NR2B NMDA receptor
• Receptors, N-Methyl-D-Aspartate

Topics

• Biomarkers, Tumor
• Cell Line, Tumor
• Cell Proliferation
• DNA Methylation
• Down-Regulation
• Epithelium (metabolism, pathology)
• Gene Expression Regulation, Neoplastic
• Health
• Humans
• Neoplasm Staging
• Polymerase Chain Reaction
• Promoter Regions, Genetic (genetics)
• Receptors, N-Methyl-D-Aspartate (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism, pathology)