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Reciprocal regulation of FOXO3a and Wnt/β-catenin signal pathways in gastric epithelial cells by H. pylori

Other Titles
 헬리코박터 필로리 감염 위상피세포에서의 FOXO3a 와 Wnt/β-catenin 신호 상호조절 
Authors
 이상헌 
Issue Date
2012
Description
Dept. of Medical Science/박사
Abstract
The bacterial pathogen, Helicobacter pylori (H. pylori) infects half of the world’s population. It chronically infects the human gastric mucosa and is the leading risk factor for the development of gastric cancer. H. pylori-cytotoxin-associated protein A (CagA) is believed to play an important role in gastric carcinogenesis. But its mechanism is still unclear. The contribution of the Wnt pathway has been extensively characterized in embryogenesis, carcinogenesis, differentiation, and stem cell biology. The forkhead box (FOXO) transcription factors play a variety of roles in diverse physiological processes including cellular differentiation, tumor suppression, metabolism, cell cycle arrest, cell death and protection from stress. FOXO3a has been shown to be associated with tumor suppression activity and inhibition of FOXO3a expression promotes cell transformation, tumor progression and angiogenesis. Thus, FOXO3a functions as a bona fide tumor suppressor. The purpose of this study was to understand the molecular mechanism underlying H. pylori related gastric carcinogenesis. We investigated the relationship between Wnt/β-catenin and FOXO3a signaling pathways and elucidated the correlation of these pathways with the carcinogenic reach underlying gastric carcinogenesis associated with H. pylori infection. H. pylori infection down regulated FOXO3a expression in gastric epithelial cells in CagA dependent manner, and induced nuclear exclusion of FOXO3a while reciprocally activating the Wnt/β-catenin signal pathway in CagA-dependent manner. FOXO3a-mediated expression of downstream genes was inhibited by H. pylori infection in gastric epithelial cells. H. pylori-mediated nuclear exclusion of FOXO3a was regulated by the ERK pathway and is dependent on CagA expression. Taken together, this study elucidates a novel pathway in cell growth and tumorigenesis that involves reciprocal regulation of FOXO3a and Wnt/β-catenin pathways by CagA of H. pylori.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000118816
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/133825
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