Cathepsin D, IGF-II and EFABP promotes breast cancer progression in African Amer.

组织蛋白酶 D、IGF-II 和 EFABP 促进非洲裔美国人的乳腺癌进展。

• 批准号: 7547695
• 负责人: Daisy DeLeon
• 金额: $ 24.3万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7547695
• 关键词: African American; athymic mouse; breast neoplasms; cathepsin D; fatty acid binding protein; health disparity; human tissue; insulinlike growth factor; minority institution research support; molecular oncology; oxidative stress

The disparity in survival among African American (AA) women affected by breast cancer is associated with poorly known clinical and pathological characteristics. A comprehensive molecular approach to understand the biological basis related to the increased mortality and poorer prognosis in this ethnic group is needed to eliminate differences in outcomes among AA patients. We propose to address this need by demonstrating that IGF-II, EFABP and cathepsin D (CD) are associated with the disparity observed in AA breast cancer patients outcome. The hypothesis underlying this proposal is that increased IGF-II and cathepsin D caused by oxidative stress and lack of EFABP promotes rapid tumor growth and metastasis resulting in a survival disparity. The specific aims of the proposal are: 1) Demonstrate that higher levels of CD and IGF-II are present in normal and breast tumor tissues of AA patients as compared to tissues from Caucasian patients; 2. Demonstrate that CD and IGF-II are highly expressed in breast cancer cells established from AA patients in vitro and that increase in these proteins promotes rapid tumor growth and metastasis in an animal model in vivo; 3. Demonstrate that the expression of EFABP is reduced in normal tissues from AA breast cancer patients as compared to tissues from Caucasian patients.Our purpose is to demonstrate that higher levels of IGF-II and cathepsin D are present in paired tissues from AA breast cancer patients and that their expression correlates with decreased survival. We will further test our hypothesis in vitro and in vivo. Analysis in vitro of the breast cancer cells established from AA patients will allow us to identify the specific forms of IGF-II and CD secreted by these cells as compared to forms secreted from cells from Caucasian patients. Higher molecular forms of IGF-II and CD are associated with glycosylation and are more potent in promoting tumor progression. The in vivo animal model will allow us to characterize the progression of the disease. Correlation of CD, IGF-II and EFABP with disease progression will provide much needed insight in understanding the mechanisms of how differential expression of these factors may account for the disparity in survival outcomes observed in AA breast cancer patients. The technical objectives, research design, and methods for this proposal will confirm, expand, and extend these preliminary findings. The hypothesis will be supported if these technical objectives are achieved.

非裔美国人（AA）乳腺癌妇女的生存差异与以下因素有关： 临床和病理特征知之甚少。一个全面的分子方法来理解 需要与该种族群体死亡率增加和预后较差相关的生物学基础， 消除AA患者之间的结果差异。我们建议通过以下方式满足这一需求： IGF-II、EFABP和组织蛋白酶D（CD）与AA乳腺癌中观察到的差异相关， 患者结局。这一假设的基础是IGF-II和组织蛋白酶D的增加导致了 通过氧化应激和缺乏EFABP促进肿瘤快速生长和转移，导致存活 差距该提案的具体目标是：（1）表明更高级别的裁谈会和第二届政府间论坛是 与来自高加索人患者的组织相比，存在于AA患者的正常和乳腺肿瘤组织中; 2.证明CD和IGF-II在AA患者建立的乳腺癌细胞中高度表达 且这些蛋白质增加促进了动物模型中的快速肿瘤生长和转移 体内; 3.证明EFABP在AA乳腺癌正常组织中的表达降低 我们的目的是证明高水平的 IGF-II和组织蛋白酶D存在于AA乳腺癌患者的配对组织中， 与生存率下降有关。我们将进一步测试我们的假设在体外和体内。体外分析 从AA患者中建立的乳腺癌细胞将使我们能够识别IGF-II的特定形式， 这些细胞分泌的CD与高加索患者细胞分泌的CD相比。更高 IGF-II和CD的分子形式与糖基化相关，并且在促进肿瘤方面更有效 进展体内动物模型将使我们能够表征疾病的进展。 CD、IGF-II和EFABP与疾病进展的相关性将提供急需的见解， 了解这些因素的差异表达如何解释差异的机制 在AA乳腺癌患者中观察到的生存结局。技术目标、研究设计和 本提案的方法将确认、扩展和扩展这些初步发现。假设是 如果这些技术目标得以实现，