Abstract
To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer (NSCLC) and its association with clinical pathological parameters, and to explore the relationship between downregulation of E-cadherin gene expression and the methylation status of its promoter region. Nested methylation-specific PCR was performed to examine CpG methylation within the 5' CpG island of the E-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lung cancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Of thirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with the corresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the 12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayed reduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA was unavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene. These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of NSCLC.
Highlights
The E-cadherin gene (CDH1) is located on human chromosome at 16q22.1, and encodes a transmembrane glycoprotein with a molecular weight of 120 KD
Downregulation of E-cadherin gene expression significantly correlated with the promoter methylation status of this gene
These results provide strong evidence that the methylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, and may play a role in the development and progression of non-small cell lung cancer (NSCLC)
Summary
The E-cadherin gene (CDH1) is located on human chromosome at 16q22.1, and encodes a transmembrane glycoprotein with a molecular weight of 120 KD. It is often expressed on the surface of most epithelial cells and localizes in the center of cytoplasm. Recent studies have found downregulation of E-cadherin gene expression in non-small cell lung cancer (NSCLC) patients of different races (Kase et al, 2000; Fei et al, 2002). E-Cadherin was reported to be downregulated and closely related to tumor invasion and metastasis in many cancers (Guarino, 2007; Mărgineanu et al, 2008; Alves et al, 2009)
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