Premium
Quantitative hypermethylation of NMDAR2B in human gastric cancer
Author(s) -
Liu JunWei,
Kim Myoung Sook,
Nagpal Jatin,
Yamashita Keishi,
Poeta Luana,
Chang Xiaofei,
Lee Juna,
Park Hannah Lui,
Jeronimo Carmen,
Westra William H.,
Mori Masaki,
Moon Chulso,
Trink Barry,
Sidransky David
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22934
Subject(s) - cancer , demethylating agent , methylation , dna methylation , biology , cancer research , medicine , oncology , gene expression , genetics , gene
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. © 2007 Wiley‐Liss, Inc.