The expression of ADAM23 and its correlation with promoter methylation in non‐small‐cell lung carcinoma

甲基化 免疫组织化学 肺癌 化学 DNA甲基化 分子生物学 癌症研究 发起人 基因表达 病理 生物 基因 免疫学 医学 生物化学
作者
Chunyan Hu,Hui Lv,Guoqing Pan,Hui-qiu Cao,Zhenghao Deng,Chuanyu Hu,Jifang Wen,Jianhua Zhou
出处
期刊:International Journal of Experimental Pathology [Wiley]
卷期号:92 (5): 333-339 被引量:17
标识
DOI:10.1111/j.1365-2613.2011.00766.x
摘要

Summary ADAM23, a member of a disintegrin and metalloprotease (ADAM) family, has been reported to be expressed in several types of tumours. The exact role of ADAM23 and the possible mechanisms in which it is involved in non‐small‐cell lung carcinoma (NSCLC) remains unclear. Therefore, this study was designed to explore the expression of ADAM23 and its correlation with promoter methylation in NSCLC. Immunohistochemistry and RT‐PCR together with Western blotting methods were used to analyse the expression of ADAM23 in 52 cancer tissue samples and eight benign pulmonary lesions as well as four cell lines. The methylated status of ADAM23 gene was determined with methylation‐specific PCR (MSP). The results of immunohistochemistry showed that the expression of ADAM23 protein was lower in NSCLC than that in corresponding normal tissues and benign pulmonary lesions (38.5% vs. 86.5% and 87.5%, P < 0.05), and decreased as NSCLC progressed. Meanwhile, methylation of ADAM23 gene was observed in 21 of 52 NSCLC tissues (40.4%), much higher than that of adjacent normal tissues (7.6%) and benign pulmonary lesions (0/8). In the cancer tissues of ADAM23‐negative samples, the rate of ADAM23 gene methylation was 50.3% (17/32). ADAM23 expression and its promoter methylation were negatively associated ( r = −0.328, P = 0.017). Moreover, weak expression of ADAM23 in methylated cancer cells increased after treatment with 5‐aza‐2′‐deoxycytidine (5‐Aza‐2′‐dC), confirming that methylation was responsible for the gene downregulation. Our results demonstrate that the expression level of ADAM23 is likely to be involved in the progression of NSCLC and its downregulation is probably correlated with promoter methylation. These findings may provide potential diagnostic and prognostic information about NSCLC.

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