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Chinese Journal of Oncology ; (12): 658-663, 2012.
Article in Chinese | WPRIM | ID: wpr-307321

ABSTRACT

<p><b>OBJECTIVE</b>To observe the expression of SFRP1 gene methylation in non-small cell lung cancer (NSCLC), and study the effect of 5-Aza-2-deoxycytidine (5-Aza-CdR) on DNA methylation and expression of SFRP1, p16 and MGMT genes in the human lung cancer cell line SPC-A-1 cells.</p><p><b>METHODS</b>SP immunohistochemistry and methylation-specific PCR were used to detect the SFRP1 methylation in 60 NSCLC cases, and 21 cases of benign lung diseases were used as control group. SPC-A-1 cells were cultured and treated with 5-Aza-CdR. The promoter methylation status of SFRP1, p16 and MGMT genes were detected by methylation-specific polymerase (MSP) chain reaction, and mRNAs were detected by real-time PCR.</p><p><b>RESULTS</b>The positive rate of SFRP1 gene methylation in NSCLC was significantly higher than that in normal lung tissue (58.3% vs. 14.3%; χ(2) = 12.118, P = 0.001). SFRP1 gene methylation was closely correlated with lymph node metastasis and degree of differentiation in NSCLC (P < 0.05). SFRP1 protein expression was correlated with clinical stage, degree of differentiation and lymph node metastasis in NSCLC (P < 0.05). The positive expression of SFRP1 protein in 30 cases of NSCLC tissue containing SFRP1 gene methylation was significantly higher than that in non-methylated NSCLC (68.6% vs. 24.0%; χ(2) = 9.613, P = 0.002). SFRP1 gene methylation was closely correlated with SFRP1 gene protein expression in NSCLC (P < 0.05). Negative expression of SFRP1 protein was correlated with the differentiation, clinical stage, and lymph node metastasis in NSCLC (all P < 0.05). Without 5-Aza-CdR treatment, the expressions of methylation of SFRP1, p16 and MGMT genes and their mRNA were low. After 5-Aza-CdR treatment at different concentrations, their expressions were significantly elevated (all P < 0.05).</p><p><b>CONCLUSIONS</b>SFRP1 gene methylation is closely associated with carcinogenesis and development of NSCLC. 5-Aza-CdR may reverse the methylation of SFRP1, p16 and MGMT genes, and facilitate the re-expression of the anti-oncogenes.</p>


Subject(s)
Antimetabolites, Antineoplastic , Pharmacology , Azacitidine , Pharmacology , Carcinoma, Non-Small-Cell Lung , Metabolism , Pathology , Cell Differentiation , Cell Line, Tumor , Cyclin-Dependent Kinase Inhibitor p16 , Genetics , Metabolism , DNA Methylation , DNA Modification Methylases , Genetics , Metabolism , DNA Repair Enzymes , Genetics , Metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Intercellular Signaling Peptides and Proteins , Genetics , Metabolism , Lung Neoplasms , Metabolism , Pathology , Lymphatic Metastasis , Male , Membrane Proteins , Genetics , Metabolism , Neoplasm Staging , RNA, Messenger , Metabolism , Tumor Suppressor Proteins , Genetics , Metabolism
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