Esophageal Cancer
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Feb 21, 2008; 14(7): 1044-1052
Published online Feb 21, 2008. doi: 10.3748/wjg.14.1044
Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma
Paras Jethwa, Mushal Naqvi, Robert G Hardy, Neil A Hotchin, Sally Roberts, Robert Spychal, Chris Tselepis
Paras Jethwa, Mushal Naqvi, Sally Roberts, Chris Tselepis, CRUK Institute for Cancer Studies, University of Birmingham, United Kingdom
Robert G Hardy, Department of Clinical and Surgical Sciences, Royal Infirmary of Edinburgh, United Kingdom
Neil A Hotchin, School of Biosciences, University of Birmingham, United Kingdom
Robert Spychal, Sandwell and West Birmingham Hopsitals NHS Trust, Birmingham, United Kingdom
Author contributions: Jethwa P and Naqvi M performed the majority of experiments; Hardy RG, Hotchin NA, and Roberts S provided vital reagents and analytical tools and were also involved in editing the manuscript; Spychal R co-ordinated and provided the collection of all the human material in addition to providing financial support for this work; Tselepis C designed the study and wrote the manuscript.
Correspondence to: Dr. Chris Tselepis, CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom. c.tselepis@bham.ac.uk
Telephone: +44-121-4142972
Fax: +44-121-6272384
Received: October 24, 2007
Revised: December 14, 2007
Published online: February 21, 2008
Abstract

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 localization 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 localization 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.

Keywords: Slug, Oesophagus, Cancer, Barrett’s metaplasia, Epithelial-mesenchymal transition