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Published on: November 23, 2013
Aberrant methylation of N-methyl-D-aspartate receptor type 2B (NMDAR2B) in non-small cell carcinoma
Hajime Tamura1, Makoto Suzuki, Yasumitsu Moriya
1Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoh-Ku, Chiba 280-8670, Japan.
Background:
N-methyl-D-aspartate receptors (NMDAR) act as tumor suppressors of digestive malignancies. The expression and genetic methylation patterns of NMDAR2B in non-small cell lung cancer (NSCLC) are unknown.
Methods:
The relationship between gene methylation and expression of NMDAR2B was analyzed in NSCLC cell lines (N = 9) and clinical tissues (N = 216). The cell lines were studied using RT-PCR and 5-aza-2'-deoxycytidine treatment, while the clinical tissues were examined by methylation specific real-time quantitative PCR and immunohistochemistry. Retrospective investigation of patient records was used to determine the clinical significance of NMDAR2B methylation.
Results:
NMDAR2B was silenced in five of the nine cell lines; 5-aza-2'-deoxycytidine treatment restored expression, and was inversely correlated with methylation. Aberrant methylation of NMDAR2B, detected in 61% (131/216) of clinical NSCLC tissues, was inversely correlated with the status of protein expression in 20 randomly examined tumors. Aberrant methylation was not associated with clinical factors such as gender, age, histological type, or TNM stage. However, aberrant methylation was an independent prognostic factor in squamous cell carcinoma cases.
Conclusions:
Aberrant methylation of the NMDAR2B gene is a common event in NSCLC. The prognosis was significantly better for cases of squamous cell carcinoma in which NMDAR2B was methylated. It may have different roles in different histological types.
Insights
Aberrant methylation of the N-methyl-D-aspartate receptor 2B (NMDAR2B) gene is common in non-small cell lung cancer (NSCLC). Methylation correlates with better prognosis in squamous cell carcinoma, suggesting a varied role in different NSCLC types.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- N-methyl-D-aspartate receptors (NMDAR) function as tumor suppressors in digestive cancers.
- NMDAR2B expression and methylation patterns in non-small cell lung cancer (NSCLC) remain uncharacterized.
Purpose of the Study:
- To investigate the relationship between NMDAR2B gene methylation and its expression in NSCLC.
- To determine the clinical significance of NMDAR2B methylation in NSCLC patients.
Main Methods:
- Analysis of NMDAR2B methylation and expression in 9 NSCLC cell lines and 216 clinical NSCLC tissues.
- Utilized RT-PCR, 5-aza-2'-deoxycytidine treatment, methylation-specific quantitative PCR, and immunohistochemistry.
- Retrospective analysis of patient records to assess clinical significance.
Main Results:
- NMDAR2B was silenced in 5/9 cell lines, with expression restored by 5-aza-2'-deoxycytidine, indicating inverse correlation with methylation.
- Aberrant NMDAR2B methylation occurred in 61% of NSCLC tissues, inversely correlating with protein expression.
- Aberrant methylation was an independent prognostic factor in squamous cell carcinoma but not associated with other clinical factors.
Conclusions:
- Aberrant methylation of NMDAR2B is a frequent event in NSCLC.
- NMDAR2B methylation is associated with a significantly better prognosis in squamous cell carcinoma cases.
- The role of NMDAR2B may differ across various NSCLC histological subtypes.
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