Tumour necrosis factor-α in Barrett's oesophagus: A potential novel mechanism of action

Chris Tselepis, Ian Perry, Christopher Dawson, Robert Hardy, SJ Darnton, Christopher McConkey, RC Stuart, N Wright, R Harrison, Janusz Jankowski

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Barrett's metaplasia (BM) is an early lesion in the progression from oesophageal inflammation through dysplasia to the development of Barrett's adenocarcinoma (BA). Previous work indicates that BM and BA are associated with reduced E-cadherin expression and increased cytoplasmic/nuclear pools of its associated protein beta-catenin. beta-catenin participates in Wnt signalling and activates oncogene transcription by complexing with T-cells factors (TCF). One such oncogene is c-myc. We have previously shown that TNF-alpha can down-regulate E-cadherin expression. Here, we assess TNF-alpha expression in Barrett's metaplasia and examine if TNF-alpha can promote beta-catenin mediated transcription of oncogenes in a gastrointestinal model system. Employing immunohistochemistry and Western blot analysis of oesophageal tissue, epithelial expression of TNF-alpha increases with progression along the metaplasia-dysplasia-carcinoma sequence (P
Original languageEnglish
Pages (from-to)6071-6081
Number of pages11
JournalOncogene
Volume21
Issue number39
DOIs
Publication statusPublished - 5 Sep 2002

Keywords

  • tumour necrosis factor-alpha (TNF-alpha)
  • cadherins and catenins
  • cancer
  • Barrett's oesophagus

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