Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Watts, G.S. et al.

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

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

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.[1]

References

Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. Watts, G.S., Tran, N.L., Berens, M.E., Bhattacharyya, A.K., Nelson, M.A., Montgomery, E.A., Sampliner, R.E. Int. J. Cancer (2007) [Pubmed]

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