COBRE: RIH: THEME A: FETAL PROTEINS & PHENOTYPES IN CANCER: COLON CARCINOMA

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。 背景和目标 越来越多的证据表明，肥胖会增加患结肠癌的风险，但其潜在的分子机制还不是很清楚。氧化应激似乎是这一过程中的一个主要因素。我们假设结肠癌的发生将受到解偶联蛋白-2(UCP2)的影响，解偶联蛋白-2是一种线粒体阴离子载体，参与产生活性氧(ROS)。为了批判性地检验这一假设，我们使用了体外和体内的实验范式。此外，我们正在评估UCP2在人源性结肠癌中的表达与各种肿瘤标志物和参与结肠癌发生的因素之间的相关性。 散发性结肠癌的发展和生长是美国重大死亡率的原因之一，细胞内活性氧簇(ROS)水平对其有很大影响。线粒体是ROS的主要来源。解偶联蛋白-2(UCP2)控制线粒体ROS的产生并减少氧化应激，但这种能力与癌细胞生物学的相关性尚不清楚。假设UCP2调控结肠癌的发生和发展。 在对12个区域金融机构进行竞争性审查后，该项目于2006年1月终止。(见项目评估报告部分)巴菲博士获得了罗德岛医院颁发的支持6个月研究的“过渡奖”。

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. Background and Aims Evidence is accumulating that obesity increases the risk of colon cancer but the underlying molecular mechanisms are not well known. Oxidative stress appears to be a major factor in this process. We hypothesize that colon carcinogenesis will be affected by uncoupling protein-2 (UCP2), a mitochondrial anion carrier involved in producing reactive oxygen species (ROS). To critically test this hypothesis, we are using in vitro and in vivo experimental paradigms. In addition, we are evaluating the correlation between UCP2 expression in human-derived colon cancer and various tumor markers and factors involved in colon carcinogenesis. Development and growth of sporadic colon cancer, a cause of significant mortality in the US, is greatly affected by intracellular levels of reactive oxygen species (ROS). Mitochondria are the primary source of ROS. Uncoupling protein-2 (UCP2) controls mitochondrial ROS production and reduces oxidative stress, but the relevance of this ability to the biology of cancer cells remains unclear. It is hypothesized that UCP2 modulates the initiation and progression of colon cancer. This project was terminated in Jan. 2006 after a competitive review of 12 RFAs. (see Program Evaluation Report section) Dr. Baffy received a "transition award" from Rhode Island Hospital to support 6 months of research.