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

TitleIdentification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma.
Publication TypeJournal Article
Year of Publication2007
AuthorsWatts GS, Tran NL, Berens ME, Bhattacharyya AK, Nelson MA, Montgomery EA, Sampliner RE
JournalInt J Cancer
Volume121
Issue10
Pagination2132-9
Date Published2007 Nov 15
ISSN1097-0215
KeywordsAdenocarcinoma, Biopsy, Cell Line, Disease Progression, Esophageal Neoplasms, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Neoplasm Invasiveness, Receptors, Tumor Necrosis Factor, RNA, Messenger
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.

DOI10.1002/ijc.22898
Alternate JournalInt. J. Cancer
PubMed ID17594693
Grant ListP30 CA023074 / CA / NCI NIH HHS / United States
CA95060 / CA / NCI NIH HHS / United States
ES06694 / ES / NIEHS NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
CA023074-26 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
George Watts, Ph.D.