Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer
| Autor: | Wei Kang, Jun Yu, Junhong Zhao, Joanna Hm Tong, Enders Kw Ng, Minnie Y. Go, Ka Fai To, Joseph J.Y. Sung, Yujuan Dong, P.W.Y. Chiu, Alfred Sl Cheng |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
MAPK8 molecular regulator Bioinformatics STAT3 Western blot Medicine PDPN medicine.diagnostic_test biology Helicobacter pylori business.industry Intestinal metaplasia Cancer biology.organism_classification medicine.disease bacterial infections and mycoses Oncology gastric carcinogenesis Cancer research Immunohistochemistry Gastritis medicine.symptom business Research Paper |
| Zdroj: | Oncoscience |
| ISSN: | 2331-4737 |
| Popis: | BACKGROUND Helicobacter pylori (H. pylori) is the most important gastric carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis through STAT3 activation are largely unknown. We evaluated the effects of H. pylori infection on STAT3 activation and dissected the signalling network of STAT3 in H. pylori- infected gastric carcinogenesis. METHODS The expression of phospho-STAT3 (pSTAT3) was evaluated by immunohistochemistry and western blot. Gene expression array and chromatin immunoprecipitation were used to dissect the STAT3 signalling network on H. pylori co-cultured AGS. RESULTS pSTAT3 was significantly higher in H. pylori -positive gastritis than in H. pylori -negative gastritis ( P = 0.003). In addition, 98% of H. pylori positive intestinal metaplasia specimens showed STAT3 activation, whereas pSTAT3 was significantly decreased in all 43 specimens one year after H. pylori eradication ( P < 0.001). Moreover, pSTAT3 was only detected in the H. pylori -infected gastric tissues of mice but not in control mice. We further identified 6 candidates ( BRUNOL4, FGFR1, SHOX2, JAK3, MAPK8, and PDPN ) were directly up-regulated by H. pylori induced STAT3 activation. CONCLUSION H. pylori infection triggers the activation of STAT3 and de-regulates multitude of tumorigenic genes which may contribute to the initiation and progression of gastric cancer. |
| Databáze: | OpenAIRE |
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