Validation and functional analysis of TNFRSF12A/Fn14 and Cyr61 in esophageal adenocarcinoma Free

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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 over-expression 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 two of the three EAC cell lines. From the list of potential targets we selected TNFRSF12A/Fn14/TWEAK receptor, a tumor necrosis factor super-family receptor and Cyr61, a integrin ligand, for further validation based on their reported roles in tumor cell survival and invasion as well as potential as novel targets for therapy. Protein expression was confirmed in SEG-1, BIC-1, and TE-7 cell lines as well as in clinical samples using immunohistochemistry. Invasion assays were used to investigate the function roles the proteins may play in tumor progression.