Shirin H, Sordillo E M, Oh S H, Yamamoto H, Delohery T, Weinstein I B, Moss S F
Department of Medicine, St. Luke's-Roosevelt Hospital Center, New York, New York 10025, USA.
Cancer Res. 1999 May 15;59(10):2277-81.
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.
幽门螺杆菌感染在流行病学上与胃癌的发生有关。为了更好地理解幽门螺杆菌在致癌过程中的作用，我们研究了幽门螺杆菌对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、产毒的、cagA阳性的幽门螺杆菌诱导AGS细胞凋亡，并在G1-S期抑制细胞周期进程。这些效应在通过血清饥饿同步化然后通过重新添加血清刺激其进入细胞周期的AGS细胞中最为明显。一个同基因的cagA阴性突变幽门螺杆菌产生了类似的效应。与5-氟尿嘧啶诱导的变化不同，幽门螺杆菌引起的从G1期到S期的细胞周期进程抑制并未伴随p53或p21cip1的持续变化，但与p27kip1表达降低以及c-fos血清反应元件转录激活受抑制有关。我们的结果表明，幽门螺杆菌在G1-S期抑制细胞周期进程并诱导凋亡，这与AGS胃癌细胞中p27kip1表达降低有关。在体内，幽门螺杆菌感染产生的类似效应可能导致非肿瘤性胃上皮细胞潜在有害的代偿性过度增殖。
