934 Immune Factors Involved in the Promotion of Esophageal Adenocarcinoma As Defined by siRNA Library Screening

BACKGROUND: Esophageal adenocarcinoma (EAC) is a classic example of inflammationassociated cancer, which develops through GERD (gastro-esophageal reflux disease)-Barrett's esophagus (BE)-dysplasia-adenocarcinoma sequence. The incidence rate for EAC has increased 4-10% per year among men since 1976 in the USA, more rapidly than for any other type of cancer. Patients with Barrett's esophagus can progress to dysplasia and EAC at 30-60 times that of the general population. NF-kB plays a key role in inflammation process and TNF-α is a pro-inflammatory cytokine and a known NF-kB activator. It has been reported that TNF-α and TNFR1 are significantly increased in BE and EACs. Glutathione Peroxidase 7 (GPX7), a recent member of GPX family which currently has 8 members, is frequently silenced through location-specific hypermethylation during Barrett's tumorigenesis. Its functions remain largely uncharacterized. In this study, we investigated the potential role of GPX7 in regulating NF-kB activity. METHODS and RESULTS: In vitro experiments and de-identified human tissue samples were utilized for quantitative real-time PCR, immunofluorescence, luciferase reporter, immunoblotting and intracellular ROS (reactive oxygen species) assays. Reconstitution of GPX7 in BE and EAC cell models abrogated TNF-αinduced NF-kB reporter activity and nuclear translocation of NF-kB-p65 (P