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Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma

查看全文 作　　者：Paras [1]Jethwa;Mushal [1]Naqvi;Robert G [2]Hardy;Neil A [3]Hotchin;Sally [1]Roberts;Robert [4]Spychal;Chris [1]Tselepis 高影响力作者 机构地区：[1]CRUK Institute for Cancer Studies,University of Birmingham,United Kingdom;[2]Department of Clinical and Surgical Sciences,Royal Infirmary of Edinburgh,United Kingdom;[3]School of Biosciences,University of Birmingham,United Kingdom;[4]Sandwell and West Birmingham Hopsitals NHS Trust,Birmingham,United Kingdom高影响力机构 出　　处：《World Journal of Gastroenterology》索引2008年第14卷第7期,共9页高影响力期刊 基　　金：Supported by City Hospital Trust Fund;the University of Birmingham Scientific Project Grant 摘　　要：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 (RT-PCR). 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. 关 键 词：食管癌 上皮间叶细胞 超声检查 治疗方法
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