Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells.
Helicobacter pylori inhibits the G1 to S transition in AGS gastric epithelial cells.
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发表时间：
1999-05
期刊：
影响因子：
11.2
通讯作者：
H. Shirin;E. Sordillo;S. Oh;H. Yamamoto;T. Delohery;I. Weinstein;S. Moss
中科院分区：
文献类型：
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作者：
H. Shirin;E. Sordillo;S. Oh;H. Yamamoto;T. Delohery;I. Weinstein;S. Moss
幽门螺杆菌感染在流行病学上与胃癌的发生有关。为了更好地理解H的作用。pylori在肿瘤发生中的作用，我们研究了H. pylori对AGS胃癌细胞系中细胞周期相关事件的影响。在共培养过程中，野生型、转基因、cagA阳性H. pylori可诱导AGS细胞凋亡，并抑制细胞周期G1-S期进程。这些作用在通过血清剥夺同步化的AGS细胞中最明显，然后通过再喂养刺激细胞周期的进展。一个cagA阴性的同基因突变体H. pylori，产生类似的效果。与5-氟尿嘧啶引起的细胞周期变化相反，H. pylori感染并不伴随p53或p21 cip 1的持续变化，但与p27 kip 1表达减少和c-fos血清反应元件转录激活抑制有关。结果表明，H. pylori可抑制胃癌细胞G1-S期的细胞周期进程并诱导细胞凋亡，与p27 kip 1表达降低有关。在体内，H. pylori感染可能导致非肿瘤性胃上皮细胞的潜在有害的代偿性过度增殖。
Infection with the bacterium Helicobacter pylori is associated epidemiologically with development of gastric cancer. To better understand the role of H. pylori in carcinogenesis, we examined the effects of H. pylori on cell cycle-related events in the AGS gastric cancer cell line. During coculture, wild-type, toxigenic, cagA-positive H. pylori induced both apoptosis and inhibition of cell cycle progression at G1-S in AGS cells. These effects were most apparent in AGS cells synchronized by serum-deprivation and then stimulated to progress through the cell cycle by refeeding. An isogenic cagA-negative mutant H. pylori, produced similar effects. In contrast to changes induced by 5-fluorouracil, the inhibition of cell cycle progression from G1 to S caused by H. pylori was not accompanied by sustained changes in p53 or p21cip1, but was associated with reduced expression of p27kip1 and inhibition of transcriptional activation of the serum-response element of c-fos. Our results indicate that H. pylori inhibits cell cycle progression at G1-S and induces apoptosis, associated with reduced expression of p27kip1 in AGS gastric cancer cells. In vivo, similar effects as a result of H. pylori infection may lead to potentially deleterious compensatory hyperproliferation by nonneoplastic gastric epithelial cells.