Slug is overexpressed in gastric carcinomas and may act synergistically with SIPI and Snail in the down-regulation of E-cadherin

C. Castro Alves, E. Rosivatz, C. Schott, R. Hollweck, I. Becker, M. Sarbia, F. Carneiro, K. F. Becker

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148 Scopus citations

Abstract

Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators - Slug and E12/E47 - in primary human gastric carcinomas and to compare this with the expression of E-cadherin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p < 0.0001). Twenty-one cases (36%) showed E12/E47 up-regulation that was not significantly associated with E-cadherin down-regulation (p = 0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p = 0.0029) and with advanced pTNM stages (p = 0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p = 0.0014) and Snail in diffuse (p = 0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and, conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators.

Original languageEnglish
Pages (from-to)507-515
Number of pages9
JournalJournal of Pathology
Volume211
Issue number5
DOIs
StatePublished - Apr 2007

Keywords

  • E-cadherin
  • Epithelial-mesenchymal transition
  • Gastric carcinoma
  • Slug
  • Snail

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