Transactivation of the EGFR by AP-1 Is Induced by Helicobacter pylori in Gastric Cancer

• DOI: 10.1111/j.1572-0241.2007.01400.x
• Publication Date: 2007-07-07T09:44:19Z
• Authors: Hassan Ashktorab; Mohammad Daremipo...; Melissa Wilson; Serwat Siddiqi; Edward L. Lee; Nasser Rakhshani; Reza Malekzadeh; Alfred C. Johnson; Stephen M. Hewitt; Duane T. Smoot
• Keywords: 0303 health sciences; Helicobacter pylori; Cell Survival; Cell Culture Techniques; Adenocarcinoma; Helicobacter Infections; 3. Good health; ErbB Receptors; Transcription Factor AP-1; 03 medical and health sciences; Stomach Neoplasms; Cell Line, Tumor; Humans; Cell Proliferation; Signal Transduction

Helicobacter pylori infection of the gastric mucosa is strongly associated with gastritis, peptic ulcer disease, and cancer. However, mechanisms by which H. causes cancer are currently unknown. Binding epidermal growth factor (EGF) to its receptor (EGFR) may be important in development This interaction accelerates cell proliferation migration, triggers epithelial signaling. In this study, we investigated effects on EGFR- AP-1-mediated signal transduction pathways AGS line tissue from humans.Cells were treated death was examined at a variety time points using viability trypan blue exclusion dye assay. To investigate EGFR regulation, cells transfected full-length truncated luciferase (luc) reporter. Tissue microarray containing 44 samples biopsies pylori-positive patients analyzed for protein expression level immunohistochemistry.EGFR promoter activity increased (twofold) 3 h after treatment commenced. Using series deletion mutants, identified region that crucial transactivation pylori. determine whether AP-1 binding altered, an construct then them up 6 h. We found induced cells, while electrophoretic mobility shift assays confirmed site following treatment. c-Jun c-Fos -1,062/-900 eight- six fold, respectively, ChIP Active staining markedly infected persons, compared uninfected controls.We conclude exposure induces production through various pathways, including those mediated AP-1. Distinct activation specify subset target genes selected, involved apoptosis. consistent humans Hence, balance between apoptosis these altered response injury caused infection, leading risk