|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|
|Date Published||2007 Nov 15|
|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|
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.
|Alternate Journal||Int. J. Cancer|
|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
Identification of Fn14/TWEAK receptor as a potential therapeutic target in esophageal adenocarcinoma.
Faculty Member Reference:
George Watts, Ph.D.