Coexpression of Helicobacter pylori's proteins CagA and HspB induces cell proliferation in AGS gastric epithelial cells, independently from the bacterial infection

Antonio De Luca, Alfonso Baldi, Patrizia Russo, Anna Todisco, Lucia Altucci, Nicola Giardullo, Luigi Pasquale, Salvatore Iaquinto, Vittorio D'Onofrio, Maria Caterina Parodi, Marco G. Paggi, Gaetano Iaquinto

Research output: Contribution to journalArticle

Abstract

Adenocarcinoma of the stomach is the second most common cause of cancer mortality in the world. The purpose of this study was to evaluate the potential role in carcinogenesis of two secreted Helicobacter pylori's proteins, CagA and HspB, both shown to increase the risk of gastric carcinoma in patients infected with H. pylori-positive strain. The effects of these two proteins on cell kinetics and the ability to selectively affect the expression of cell cycle-related proteins by transfection of a human gastric epithelial cell line (AGS) were analyzed. Using a genomic library of H. pylori, we isolated and cloned CagA and HspB. The effects of the overexpression of these proteins on cell growth were analyzed in AGS cells by immunoblots, proliferation assay, and flow cytometry. Coexpression of CagA and HspB in AGS cells in the first 48 h caused an increase of the level of E2F transcription factor, cyclin D3, and phosphorylated retinoblastoma protein, all involved in the G1-S checkpoint of the cell cycle Consistently, an increase of cell proliferation, corresponding to an augment of the fraction of the cells in the S-G 2-M phase of the cell cycle, was also demonstrated. Moreover, an increase of c-jun protein levels, but not of c-fos, was also found after coexpression of CagA and HspB. All these data suggest that CagA and HspB, independently from the bacterial infection, have a direct effect on the cell growth of the gastric cells acting on the G1-S checkpoint of the cell cycle.

Original languageEnglish
Pages (from-to)6350-6356
Number of pages7
JournalCancer Research
Volume63
Issue number19
Publication statusPublished - Oct 1 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    De Luca, A., Baldi, A., Russo, P., Todisco, A., Altucci, L., Giardullo, N., Pasquale, L., Iaquinto, S., D'Onofrio, V., Parodi, M. C., Paggi, M. G., & Iaquinto, G. (2003). Coexpression of Helicobacter pylori's proteins CagA and HspB induces cell proliferation in AGS gastric epithelial cells, independently from the bacterial infection. Cancer Research, 63(19), 6350-6356.