TGF-α inhibits apoptosis of murine gastric pit cells through an NF-κB-dependent pathway

Abstract

Background & Aims: Recently, some growth factors have been shown to play roles not only as growth factors but also as cell-surviving factors. Transforming growth factor (TGF)-α is expressed in normal gastric mucosa. In this study, we investigated the cell-surviving effect of TGF-α on gastric mucosal cells and its signaling mechanism. Methods: We used a gastric mucosal cell line, GSM06, and gastric cancer cell line, AGS. Apoptosis was induced by serum depletion or exposure to sodium butyrate. Analysis of apoptosis was performed by DNA ladder assay, measuring the DNA fragmentation ratio (Burton method), and 4′,6-diamidino-2-phenylindole staining. Results: TGF-α protected gastric mucosal cells against apoptosis induced by serum depletion or sodium butyrate in a dose-dependent manner. This antiapoptotic effect of TGF-α was blocked by the pretreatment with reagents that can potentially inhibit NF-κB activation, whereas neither MEK inhibitor PD098059 nor PI-3-kinase inhibitor wortmannin abolished this effect. Electrophoretic mobility shift assay showed nuclear factor κB (NF-κB) activation by TGF-α stimulation. TGF-α also enhanced the expression of Bcl-2 family proteins in an NF-κB-dependent manner. Conclusions: TGF-α plays an antiapoptotic role in gastric mucosal cells via the NF-κB-dependent pathway.