Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma

Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma
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DOI:
10.3748/wjg.v17.i37.4225
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发表时间:
2011-10-07
影响因子:
4.3
通讯作者:
Zhang, Shu-Tian
Zhang, Shu-Tian
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Jun-Xiong;He, Yuan-Long;Zhang, Shu-Tian

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目的: 鉴定食管鳞状细胞癌 (ESCC) 中新型甲基化沉默基因 pentraxin 3 (PTX3)。 方法: 采用逆转录聚合酶链反应检测 6 种人食管鳞状细胞癌 (ESCC) 细胞系、一种人永生化正常食管上皮细胞系、原发性食管鳞状细胞癌肿瘤组织和配对的邻近非肿瘤组织中 PTX3 mRNA 的表达。 (逆转录聚合酶链反应)。使用半定量免疫组织化学来检查细胞定位和蛋白质水平。采用甲基化特异性PCR和亚硫酸氢盐基因组测序来研究候选基因的甲基化情况。结果:在大多数ESCC细胞系中,我们发现由于基因启动子高甲基化,PTX3表达下调,亚硫酸氢盐基因组测序进一步证实了这一点。用 5-aza-2'-deoxycytidine 去甲基化处理可恢复 ESCC 细胞系中 PTX3 mRNA 的表达。甲基化在肿瘤组织中 (85%) 比邻近非肿瘤组织 (25%) 更常见 (P < 0.01)。结论:PTX3 在 ESCC 中通过启动子高甲基化下调,并且有可能作为 ESCC 的生物标志物。 (C)2011年百事登。版权所有。
AIM: To identify the novel methylation-silenced gene pentraxin 3 (PTX3) in esophageal squamous cell carcinoma (ESCC).METHODS: PTX3 mRNA expression was examined in six human ESCC cell lines, one human immortalized normal esophageal epithelial cell line, primary ESCC tumor tissue, and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction (RTPCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. Methylation specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate gene.RESULTS: In the majority of ESCC cell lines, we found that PTX3 expression was down-regulated due to gene promoter hypermethylation, which was further confirmed by bisulphite genomic sequencing. Demethylation treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell lines. Methylation was more common in tumor tissues (85%) than in adjacent nontumor tissues (25%) (P < 0.01).CONCLUSION: PTX3 is down-regulated through promoter hypermethylation in ESCC, and could potentially serve as a biomarker of ESCC. (C) 2011 Baishideng. All rights reserved.