AR COBRE: PROTEIN INTERACTIONS IN CARCINOGENESIS AND CANCER TREATMENT

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。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 胰腺癌是一种非常具有侵袭性的癌症。导致胰腺癌高死亡率的主要因素之一是大多数胰腺癌患者对包括放射疗法和化学疗法在内的疗法的反应差。我们这个项目的长期目标是了解胰腺癌对治疗耐药的分子机制。我们推测参与活性氧（ROS）产生或清除的线粒体蛋白可能是胰腺细胞对治疗产生抗性的原因。 因此，我们建议使用定量蛋白质组学方法系统地筛选参与胰腺癌细胞中ROS产生和清除的线粒体蛋白，这些细胞对ROS诱导药物具有不同的敏感性。 我们特别感兴趣的是鉴定可以被ROS靶向的新型蛋白质/酶，诱导抗癌药物通过ROS介导的凋亡途径选择性地杀死癌细胞。

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. Pancreatic cancer is an exceptionally aggressive cancer. One of the major factors contributing to the high fatality of pancreatic cancer is the poor response of most pancreatic cancer patients to therapies including radiation therapy and chemotherapy. Our long-term objective of this project is to understand the molecular mechanisms underlying the resistance of pancreatic cancer to therapies. We hypothesize that the mitochondrial proteins involved in reactive oxygen species (ROS) production or scavenging may be responsible for the resistance of pancreatic cells to therapies. Accordingly, we propose to use quantitative proteomic methods to systematically screen mitochondrial proteins that are involved in ROS production and scavenging in pancreatic cancer cells with different sensitivity to ROS inducing drugs. We are especially interested in identifying novel proteins/enzymes that can be targeted by ROS, inducing anti-cancer drugs to selectively kill cancer cells through ROS mediated apoptotic pathways.