Up regulation of GW112 Gene by NF kappa B Promotes an Antiapoptotic Property in Gastric Cancer Cells

Abstract

To clarify the regulatory mechanism of GW112 gene expression, 5'-flanking region of the human GW112 gene was isolated and characterized in the present study. T-RACE analysis showed a single transcription start site, which is located 142 nucleotides upstream of the translation initiation site. Transient transfection studies with serial deletion constructs and close examination of the sequences identified a putative NF kappa B binding sequence between -442 and -430, which could be responsible for efficient expression of the GW112 gene. Indeed, GW112 gene was found to be regulated by NF kappa B signals including overexpressed p65 and I kappa B alpha, IKK inhibitor, and proteasome inhibitor. Binding of NF kappa B to its putative site was confirmed by EMSA and ChIP assays. These results suggest that NF kappa B is an essential regulatory factor for GW112 transcription. Based on this finding, we next confirmed that inhibition of GW112 expression could induce apoptosis in the presence of cytotoxic agent in gastric cancer cells, Furthermore, knocking-down or overexpression of GW112 gene in gastric cancer cells demonstrated that GW112 has an antiapoptotic property against the cytotoxic agents-induced apoptosis. Taken together, these results suggest that GW112 could be an important mediator in NF kappa B-dependent tumorigenesis of digestive tract tissues. (C) 2009 Wiley-Liss, Inc.