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

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

Research output: Contribution to journalArticle

47 Citations (Scopus)

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
Externally publishedYes

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Adenocarcinoma
Barrett Esophagus
imidazole mustard
Cell Line
Therapeutics
Cell Survival
Neoplasms
Microarray Analysis
TWEAK receptor
Disease Progression
Analysis of Variance
Proteins
Survival Rate
Tumor Necrosis Factor-alpha
Immunohistochemistry
Biopsy

Keywords

  • Esophageal adenocarcinoma
  • Fn14
  • Microarray
  • TWEAK

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Watts, G. S., Tran, N., Berens, M. E., Bhattacharyya, A. K., Nelson, M. A., Montgomery, E. A., & Sampliner, R. E. (2007). Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. International Journal of Cancer, 121(10), 2132-2139. https://doi.org/10.1002/ijc.22898

Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. / Watts, George S.; Tran, Nhan; Berens, Michael E.; Bhattacharyya, Achyut K.; Nelson, Mark A.; Montgomery, Elizabeth A.; Sampliner, Richard E.

In: International Journal of Cancer, Vol. 121, No. 10, 15.11.2007, p. 2132-2139.

Research output: Contribution to journalArticle

Watts, GS, Tran, N, Berens, ME, Bhattacharyya, AK, Nelson, MA, Montgomery, EA & Sampliner, RE 2007, 'Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma', International Journal of Cancer, vol. 121, no. 10, pp. 2132-2139. https://doi.org/10.1002/ijc.22898
Watts, George S. ; Tran, Nhan ; Berens, Michael E. ; Bhattacharyya, Achyut K. ; Nelson, Mark A. ; Montgomery, Elizabeth A. ; Sampliner, Richard E. / Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. In: International Journal of Cancer. 2007 ; Vol. 121, No. 10. pp. 2132-2139.
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