title: 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.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Myoung Sook
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Jatin
authors.initials: J
authors.lastname: Nagpal
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Keishi
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Luana
authors.initials: L
authors.lastname: Poeta
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Juna
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Hannah Lui
authors.initials: HL
authors.lastname: Park
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Carmen
authors.initials: C
authors.lastname: Jeronimo
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.affiliation: Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Tsurumibaru, Beppu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Chulso
authors.initials: C
authors.lastname: Moon
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Barry
authors.initials: B
authors.lastname: Trink
authors.affiliation: Department of Otolaryngology, Division of Head and Neck Cancer Research, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
mesh_terms: D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D015536:Down-Regulation; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006262:Health; D006801:Humans; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate