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E-钙黏蛋白启动子甲基化及β-连环蛋白突变对鼻咽癌细胞侵袭和转移的影响

[Influence of E-cadherin promoter methylation and mutation of beta-catenin on invasion and metastasis of nasopharyngeal carcinoma cells].

作者信息

Li Zhi, Lin Su-xia, Liang Ying-jie

机构信息

Department of Pathology, Sun Yat-sen Medical College, Zhong Shan University, Guangzhou 510089, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2003 May;25(3):238-42.

PMID:12839684
Abstract

OBJECTIVE

To study the mechanism of invasion and metastasis in early nasopharyngeal carcinoma (NPC) in relation to E-cadherin promoter methylation and mutation in exon 3 of beta-catenin.

METHODS

Methylation of E-cadherin promoter, mutation in exon 3 of beta-catenin and differential expression of beta-catenin in the primary lesion of 21 NPC and the metastatic lymph node of 21 NPC were investigated by DNA Methylation-Specific PCR, direct sequencing and immunohistochemical method.

RESULTS

Methylation on E-cadherin promoter was showed in 23.8% (5/21) primary lesions and 61.9% (13/21) metastatic lymph nodes (P < 0.01). Mutation in exon 3 of beta-catenin was showed in 3 of 42 tissues: codon 37 (TCT-->GCT), codon 41 (ACC-->GCC) and codon 47 (AGT-->ACT). However, there was no relation between these mutations and invasion or metastasis (P > 0.05). High beta-catenin expression on the membrane without nuclear expression was observed in 42 tissues (P > 0.05).

CONCLUSION

  1. In NPC, methylation of promoter is a major cause of down-regulation of E-cadherin which may finally lead to detachment and metastasis of neoplastic cells, 2. Mutation in exon 3 of beta-catenin is a rare event in NPC. It may be an early event in the carcinogenesis of NPC but have no significant role in invasion and metastasis and 3. High expression of beta-catenin, as one of NPC characteristics, is not a key factor for invasion or metastasis.
摘要

目的

研究早期鼻咽癌(NPC)侵袭和转移机制与E-钙黏蛋白启动子甲基化及β-连环蛋白第3外显子突变的关系。

方法

采用DNA甲基化特异性PCR、直接测序和免疫组化方法,研究21例NPC原发灶及21例NPC转移淋巴结中E-钙黏蛋白启动子甲基化、β-连环蛋白第3外显子突变及β-连环蛋白的差异表达。

结果

23.8%(5/21)的原发灶和61.9%(13/21)的转移淋巴结显示E-钙黏蛋白启动子甲基化(P<0.01)。42个组织中有3个显示β-连环蛋白第3外显子突变:密码子37(TCT→GCT)、密码子41(ACC→GCC)和密码子47(AGT→ACT)。然而,这些突变与侵袭或转移之间无相关性(P>0.05)。42个组织中观察到β-连环蛋白在细胞膜上高表达而无核表达(P>0.05)。

结论

  1. 在NPC中,启动子甲基化是E-钙黏蛋白下调的主要原因,最终可能导致肿瘤细胞脱离和转移;2. β-连环蛋白第3外显子突变在NPC中是罕见事件。它可能是NPC致癌过程中的早期事件,但在侵袭和转移中无显著作用;3. β-连环蛋白高表达作为NPC的特征之一,不是侵袭或转移的关键因素。

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The cadherin-catenin complex in nasopharyngeal carcinoma.鼻咽癌中的钙黏蛋白-连环蛋白复合体。
Eur Arch Otorhinolaryngol. 2011 Sep;268(9):1335-41. doi: 10.1007/s00405-010-1464-z. Epub 2011 Jan 15.