Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma

George S. Watts, Nhan L. Tran, Michael E. Berens, Achyut K. Bhattacharyya, Mark A. Nelson, Elizabeth A. Montgomery, Richard E. Sampliner

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Given the poor survival rate and efficacy of current therapy for esophageal adenocarcinoma (EAC), there is a need to identify and develop new therapeutic targets for treatment. Microarray analysis (Affymetrix U133A GeneChips, Robust Multi-Chip Analysis) was used to expression profile 11 normal squamous and 18 Barrett's esophagus biopsies, 7 surgically resected EACs and 3 EAC cell lines. Two hundred transcripts representing potential therapeutic targets were identified using the following criteria: significant overexpression in EAC by analysis of variance (p = 0.05, Benjamini Hochberg false discovery rate); 3-fold increase in EAC relative to normal and Barrett's esophagus and expression in at least 2 of the 3 EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor, for further validation based on its reported role in tumor cell survival and potential as a target for therapy. Fn14 protein expression was confirmed in SEG-1 and BIC-1 cell lines, but Fn14 was not found to affect tumor cell survival after exposure to chemotherapeutics as expected. Instead, a novel role in EAC was discovered in transwell assays, in which modulating Fn14 expression affected tumor cell invasion. Fn14's potential as a therapeutic target was further supported by immunohistochemistry on a tissue microarray of patient samples that showed that Fn14 protein expression increased with disease progression in EAC.

Original languageEnglish (US)
Pages (from-to)2132-2139
Number of pages8
JournalInternational Journal of Cancer
Volume121
Issue number10
DOIs
StatePublished - Nov 15 2007

Keywords

  • Esophageal adenocarcinoma
  • Fn14
  • Microarray
  • TWEAK

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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