Dysregulation of Expression of the FOXO3 Transcription Factors Pathway in Helicobacter pylori Associated Gastric Cancer

Abstract

The transcription factor FOXO3 acts as a tumor suppressor and is the major target of AKT kinases pathway. The protein encoded by FOXO3, prevents the activation of genes that are important for proliferation, differentiation and death cell. In addition, FOXO3 interacts with BCL-2 family proteins; and among them, BBC3 (PUMA) and BCL2L (BIM) are responsible for regulating apoptosis through the BAX and BAK chains. This study investigated the expression of FOXO3a, BBC3 and BCL2L in gastric cancer considering the presence of Helicobacter pylori and its involvement in the modulation of gene and protein expression. A total of 225 gastric biopsy samples were evaluated from individuals with normal gastric mucosa (n=54), gastritis (n=108), and gastric cancer (n=63), of both genders and over 18 years old. Samples were subclassified according to the presence or absence of Helicobacter pylori, detected by PCR. Real-time quantitative RT-PCR (qRT-PCR) and western blotting, were used to detect the expression. FOXO3 showed increased gene (p<0.0001) and protein (p=0.036) expression in patients with gastric cancer, who also exhibited a boost in mRNA expression through H. pylori infection. BCL2L had a subtle increase in its expression independent of the presence of H. pylori (p<0.0001), while the BBC3 gene showed no alterations. Our results suggested that increase FOXO3 expression may play an important role in carcinogenesis by performing positive feedback in an attempt to eliminate neoplastic cells. FOXO3 could be suggested a prognostic marker as well as a potential molecular therapy target for gastric cancer patients.