Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma
Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma
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DOI：
10.3748/wjg.14.1044
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发表时间：
2008-02-21
影响因子：
4.3
通讯作者：
Tselepis, Chris
中科院分区：
文献类型：
--
作者：
Jethwa, Paras;Naqvi, Mushal;Tselepis, Chris
目的：方法：采用实时荧光定量逆转录聚合酶链反应（RTPCR）检测食管癌组织和Barrett化生组织中E-cadherin、Slug、Snail和Twist mRNA的表达。半定量免疫组织化学用于检查细胞定位和蛋白质水平。通过将Slug转染到腺癌细胞系OE 33中来检查Slug对上皮间质转化（EMT）标志物的影响。结果：Slug在巴雷特化生中的细胞定位主要是细胞质，而在腺癌中则是细胞核。半定量分析表明，与匹配的Barrett化生标本相比，Slug在腺癌中更丰富，Snail和Twist在腺癌中表达，但与Barrett粘膜相比，它们在细胞质中表达，并且不被诱导。这些观察结果得到了mRNA研究的支持，其中只有Slug mRNA在腺癌中过表达，并与E-钙粘蛋白表达呈负相关。Slug在OE 33中的过表达介导了E-cadherin的抑制，并诱导了间充质标志物vimentin和fibronectin的表达。结论：腺癌的进展与Slug表达的增加有关，这可能是E-cadherin沉默的一种机制。(c)2008年WJG。All rights reserved.
AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma.METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RTPCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. The effect of Slug on epithelial mesenchymal transition (EMT) markers was examined by transfection of Slug into an adenocarcinoma line OE33.RESULTS: Cellular localisation of Slug in Barrett's metaplasia was largely cytoplasmic whilst in adenocarcinoma it was nuclear. Semi-quantitative analysis indicated that Slug was more abundant in adenocarcinoma compared to matched Barrett's metaplastic specimens, Snail and Twist were expressed in adenocarcinoma but were cytoplasmic in location and not induced compared to Barrett's mucosa. These observations were supported by mRNA studies where only Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression. Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.CONCLUSION: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing. (c) 2008 WJG. All rights reserved.