COBRE: RIH: THEME B: H PYLORI IN GASTRIC CARCINOGENESIS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 慢性H. pylori感染是胃癌最重要的危险因素，但持续的H.幽门螺杆菌定植与胃癌发生的关系尚不清楚。我们发现慢性H.胃上皮细胞的幽门螺杆菌感染导致与p27 --具有肿瘤抑制特性的细胞周期蛋白依赖性激酶抑制剂--表达降低相关的结肠癌抗性状态。本研究探讨了H. pylori降低p27表达（目的1），确定胃上皮细胞中p27缺失的功能后果（目的2），并探索胃上皮细胞中伴随其对H. pylori诱导的细胞凋亡，作为候选胃癌生物标志物（aim 3）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic H. pylori infection is the most important risk factor for gastric cancer, but the molecular and cellular mechanisms linking sustained H. pylori colonization with gastric carcinogenesis are poorly defined. We showed that chronic H. pylori infection of gastric epithelial cells leads to a state of apoptosis-resistance associated with decreased expression of p27 - a cyclin-dependent kinase inhibitor with tumor suppressor properties. This project examines the mechanisms by which H. pylori decreases p27 expression (aim 1), determines the functional consequences of p27 loss in gastric epithelial cells (aim 2) and explores other molecular changes in gastric epithelial cells accompanying their resistant to H. pylori-induced apoptosis, as candidate gastric cancer biomarkers (aim 3).