下调和上调
交易激励
生物
幽门螺杆菌
癌症研究
表皮生长因子受体
细胞生长
癌变
MAPK/ERK通路
生长抑制
表皮生长因子
激酶
分子生物学
细胞培养
基因表达
癌症
细胞生物学
基因
生物化学
遗传学
作者
Sarah Keates,Andrew C. Keates,Sheuli Nath,Richard M. Peek,Ciarán P. Kelly
出处
期刊:Gut
[BMJ]
日期:2005-10-01
卷期号:54 (10): 1363-1369
被引量:47
标识
DOI:10.1136/gut.2005.066977
摘要
Helicobacter pylori, in particular cytotoxin associated gene (cag)+ strains, have been shown to enhance gastric epithelial cell proliferation in vivo, an effect that likely contributes to gastric carcinogenesis. Early growth response gene 1 (Egr-1) is a crucial regulator of cell growth, differentiation, and survival, which is known to play a role in carcinogenesis and cancer progression. The aims of this study were to: (1) examine whether H pylori could upregulate Egr-1 in gastric epithelial cell lines; (2) determine whether there was a differential response to infection with different strains; (3) examine the role of the cag pathogenicity island in this process; and (4) elucidate the molecular mechanisms leading to Egr-1 upregulation.We found that infection of AGS cells with cag+H pylori resulted in a rapid (1-2 hours) but transient increase in Egr-1 mRNA and protein levels whereas coculture with cag- isolates did not elicit this response. Furthermore, two independent cagE- isogenic mutants of H pylori also demonstrated impaired ability to upregulate Egr-1. Upregulation of Egr-1 protein was inhibited by the extracellular regulated kinase (ERK)1/2 inhibitor PD98059 and overexpression of dominant negative MEK1 downregulated Egr-1 luciferase reporter gene activity. Treatment of AGS cells with the epidermal growth factor receptor (EGFR) kinase inhibitors PD153035 and AG1478 resulted in a reduction in H pylori mediated Egr-1 upregulation, demonstrating that EGFR transactivation plays a role in this early cellular process.Our findings show that cag+H pylori cause rapid induction of Egr-1 in gastric epithelial cells which may contribute to H pylori mediated pathogenesis.
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