Novel effects of Helicobacter pylori CagA on key genes of gastric cancer signal transduction: a comparative transfection study.
Helicobacter pylori (H. pylori) infection is now recognized as a worldwide problem. Helicobacter pylori CagA is the first bacterial oncoprotein to be identified in relation to human cancer. Helicobacter pylori CagA is noted for structural diversity in its C-terminal region (contains EPIYA motifs), with which CagA interacts with numerous host cell proteins. Deregulation of host signaling by translocated bacterial proteins provides a new aspect of microbial-host cell interaction. The aim of this study is to compare the cellular effects of two different CagA EPIYA motifs on identified signaling pathways involve in gastric carcinogenesis. To investigate the effects of CagA protein carboxyl region variations on the transcription of genes involved in gastric epithelial carcinogenesis pathways, the eukaryotic vector carrying the cagA gene (ABC and ABCCC types) was transfected into gastric cancer cell line. The 42 identified key genes of signal transduction involved in gastric cancer were analyzed at the transcription level by real-time PCR. The results of real-time PCR provide us important clue that the ABCCC oncoprotein variant can change the fate of the cell completely different from ABC type. In fact, these result proposed that the ABCCC type can induce the intestinal metaplasia, IL-8, perturbation of Crk adaptor proteins, anti-apoptotic effect and carcinogenic effect more significantly than ABC type. These data support our hypothesis of a complex interaction of host cell and these two different H. pylori effector variants that determines host cellular fate.
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran Department of Bacteriology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-331, Tehran, Iran farzam_vaziri@yahoo.com.
Farzam
F
Vaziri
Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-331, Tehran, Iran.
Shahin N
SN
Peerayeh
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran.
Masoud
M
Alebouyeh
Neuroscience Research Center (NRC) and Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19615-1178, Tehran, Iran.
Nader
N
Maghsoudi
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran.
Pedram
P
Azimzadeh
Department of Bacteriology, Pasteur Institute of Iran, P.O. Box: 1316943551, Tehran, Iran.
Seyed D
SD
Siadat
Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box: 19835-187, Tehran, Iran.
Mohammad R
MR
Zali
D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D016480:Helicobacter pylori / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015513:Oncogene Proteins; C080866:cagA protein, Helicobacter pylori
CagA; EPIYA motif; Gastric carcinogenesis; Helicobacter pylori; cell signaling; comparative study