CagA(+) H. pylori induces Akt1 phosphorylation and inhibits transcription of p21(WAF1/CIP1) and p27(KIP1) via PI3K/Akt1 pathway.
- Author:
Shu-Ping LI
1
;
Xue-Jun CHEN
;
Ai-Hua SUN
;
Jin-Fang ZHAO
;
Jie YAN
Author Information
- Publication Type:Journal Article
- MeSH: Antigens, Bacterial; genetics; physiology; Bacterial Proteins; genetics; physiology; Cell Line; Cyclin-Dependent Kinase Inhibitor p21; biosynthesis; Cyclin-Dependent Kinase Inhibitor p27; Gastric Mucosa; cytology; enzymology; microbiology; Helicobacter pylori; metabolism; pathogenicity; physiology; Humans; Interleukin-8; secretion; Intracellular Signaling Peptides and Proteins; metabolism; Phosphatidylinositol 3-Kinases; metabolism; Phosphorylation; Proto-Oncogene Proteins c-akt; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Transcription, Genetic; Virulence
- From: Biomedical and Environmental Sciences 2010;23(4):273-278
- CountryChina
- Language:English
-
Abstract:
OBJECTIVECytotoxin-associated protein (CagA) of H. pylori has been confirmed to be closely associated with gastric inflammation and tumorigenesis, but the mechanism behind it is little understood. In this study, we try to determine roles of CagA(+) strain in activating PI3K/Akt1 signaling pathway, and affecting expression of p21(WAF1/CIP1) and p27(KIP1), and also in releasing IL-8 in host cells.
METHODSAkt1 phosphorylation and IL-8 levels of CagA(+) and CagA⁻ strain infected AGS cells were detected by ELISAs. Two quantitative RT-PCRs were established to measure p21(WAF1/CIP1) and p27(KIP1) mRNA levels in the CagA(+) and CagA⁻ strain infected cells. LY294002, an inhibitor of PI3K/Akt pathway, was used to define effect of the pathway in IL-8 release.
RESULTSCagA(+) strain could induce an obvious elevation of Akt1 phosphorylation in the infected AGS cells while CagA? strain failed to do so. The CagA(+) H. pylori strain infected AGS cells showed significant drops both in p21(WAF1/CIP1) and p27(KIP1) mRNA levels, whereas the CagA⁻ H. pylori strain caused a remarkable increase in p21(WAF1/CIP1) mRNA without affecting p27(KIP1) gene transcription in the AGS cells. Both the CagA(+) and CagA⁻ H. pylori strains enabled AGS cells to produce close elevated levels of IL-8, and the LY294002 block resulted in unexpected elevations of IL-8 levels.
CONCLUSIONSCagA can activate PI3K/Akt1 pathway that plays an inhibitory role in IL-8 release in H. pylori infected AGS cells. Activation of PI3K/Akt1 pathway and subsequent negative regulation of p21(WAF1/CIP1) and p27(KIP1) expression might be involved in CagA-associated carcinogenesis.
