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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 幽门螺杆菌慢性感染是胃癌最重要的危险因素，但幽门螺杆菌持续定植与胃癌发生之间的分子和细胞机制尚不清楚。我们发现，幽门螺杆菌慢性感染胃上皮细胞会导致一种与p27表达减少相关的凋亡抵抗状态，p27是一种具有肿瘤抑制特性的细胞周期蛋白依赖的激酶抑制物。本项目研究了幽门螺杆菌降低p27表达的机制(目标1)，确定了p27缺失在胃上皮细胞中的功能后果(目标2)，并探索了胃上皮细胞中伴随着对幽门螺杆菌诱导的凋亡的抗性的其他分子变化，作为候选的胃癌生物标志物(目标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).