Overexpression of Slug is associated with malignant progression of esophageal adenocarcinoma.
OBJECTIVE
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.


CONCLUSIONS
Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.
Jethwa
Paras
P
CRUK Institute for Cancer Studies, University of Birmingham, Vincent Drive, Birmingham B15 2TH, United Kingdom.
Naqvi
Mushal
M
Hardy
Robert G
RG
Hotchin
Neil-A
NA
Roberts
Sally
S
Spychal
Robert
R
Tselepis
Chris
C
D000230:Adenocarcinoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D001471:Barrett Esophagus / Q000150:complications / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
D015820:Cadherins; D017931:DNA Primers; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1