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- Title
Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma.
- Authors
Watts, George S.; Tran, Nhan L.; Berens, Michael E.; Bhattacharyya, Achyut K.; Nelson, Mark A.; Montgomery, Elizabeth A.; Sampliner, Richard E.
- 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. © 2007 Wiley-Liss, Inc.
- Publication
International Journal of Cancer, 2007, Vol 121, Issue 10, p2132
- ISSN
0020-7136
- Publication type
Article
- DOI
10.1002/ijc.22898