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Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma

World Journal of Gastroenterology 2008年第7期14卷 1044-1052页

作者： Paras Jethwa Mushal Naqvi Robert G Hardy neil a hotchin Sally Roberts Robert Spychal Chris Tselepis CRUK Institute for Cancer Studies University of BirminghamUnited Kingdom Department of Clinical and Surgical Sciences Royal Infirmary of EdinburghUnited Kingdom School of Biosciences University of BirminghamUnited Kingdom Sandwell and West Birmingham Hopsitals NHS Trust BirminghamUnited Kingdom

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 ***: 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 ***: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.

关键词： Slug Oesophagus Cancer Barrett's metaplasia Epithelial-mesenchymal transition

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