Title | Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Watts GS, Tran NL, Berens ME, Bhattacharyya AK, Nelson MA, Montgomery EA, Sampliner RE |
Journal | Int J Cancer |
Volume | 121 |
Issue | 10 |
Pagination | 2132-9 |
Date Published | 2007 Nov 15 |
ISSN | 1097-0215 |
Keywords | Adenocarcinoma, 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. |
DOI | 10.1002/ijc.22898 |
Alternate Journal | Int. J. Cancer |
PubMed ID | 17594693 |
Grant List | P30 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 |