TY - JOUR
T1 - Promoter-hypermethylation associated defective expression of E-cadherin in primary non-small cell lung cancer
AU - Wang, G
AU - Hu, X
AU - Lu, C
AU - Su, C
AU - Luo, S
AU - Luo, Zewei
PY - 2008/11/1
Y1 - 2008/11/1
N2 - Hypermethylation of CpG islands is well known as a major inactivation mechanism of tumor suppressor genes. E-cadherin (E-cad) as a tumor invasion suppressor has been reported in several invasive and metastatic carcinomas. However, its significance in carcinogenesis of primary non-small cell lung cancer (NSCLC) is not well documented. This study was designed to assess the significance with 95 pairs of carefully collected NSCLC tumors and corresponding nonmalignant tissue samples. We carried out PCR-SSCP (single-strand conformation polymorphism) and PCR-RFLP (restriction fragment length polymorphism) screening for DNA variants, bisulfite conversion-specific MSP for methylation analysis, reverse transcription (RT)-PCR for mRNA and immunohistochemistry (IHC) for protein expression assays. To investigate effect of promoter-hypermethylation on E-cad expression, we also did demethylation experiment in six cell lines. First, we found that the -160A carriers (a single nucleotide polymorphism (SNP) in the promoter region of E-cad) had an increased risk for lung cancer development when compared to DNA from healthy volunteers (OR (odds ratio)=2.81; 95% CI (confidence interval), 1.36-5.86). Methylation of E-cad occurred with a significantly higher frequency in tumors than corresponding normal peritumoral tissues (P
AB - Hypermethylation of CpG islands is well known as a major inactivation mechanism of tumor suppressor genes. E-cadherin (E-cad) as a tumor invasion suppressor has been reported in several invasive and metastatic carcinomas. However, its significance in carcinogenesis of primary non-small cell lung cancer (NSCLC) is not well documented. This study was designed to assess the significance with 95 pairs of carefully collected NSCLC tumors and corresponding nonmalignant tissue samples. We carried out PCR-SSCP (single-strand conformation polymorphism) and PCR-RFLP (restriction fragment length polymorphism) screening for DNA variants, bisulfite conversion-specific MSP for methylation analysis, reverse transcription (RT)-PCR for mRNA and immunohistochemistry (IHC) for protein expression assays. To investigate effect of promoter-hypermethylation on E-cad expression, we also did demethylation experiment in six cell lines. First, we found that the -160A carriers (a single nucleotide polymorphism (SNP) in the promoter region of E-cad) had an increased risk for lung cancer development when compared to DNA from healthy volunteers (OR (odds ratio)=2.81; 95% CI (confidence interval), 1.36-5.86). Methylation of E-cad occurred with a significantly higher frequency in tumors than corresponding normal peritumoral tissues (P
U2 - 10.1016/j.lungcan.2008.03.023
DO - 10.1016/j.lungcan.2008.03.023
M3 - Article
C2 - 18468719
VL - 62
SP - 162
EP - 172
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -
