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

受乳腺癌影响的非裔美国人(AA)女性的存活率差异与 临床和病理特征鲜为人知。一种全面的分子方法来理解 这需要与该民族死亡率增加和预后较差有关的生物学基础 消除再生障碍性贫血患者之间的预后差异。我们建议通过演示来满足这一需求 IGF-II、EFABP和组织蛋白酶D(CD)与AA乳腺癌的差异有关 病人结局。支持这一建议的假设是，IGF-II和组织蛋白酶D的增加导致 通过氧化应激和缺乏EFABP促进肿瘤的快速生长和转移，从而导致生存 贫富差距。该提案的具体目标是：1)表明更高水平的CD和IGF-II是 在AA患者的正常组织和乳腺肿瘤组织中的表达与高加索患者的组织相比； 2.证明再生障碍性贫血患者建立的乳腺癌细胞高表达CD和IGF-II 并在动物模型中促进肿瘤快速生长和转移 AA型乳腺癌正常组织中EFABP的表达下调 患者与高加索患者的组织进行比较。我们的目的是证明较高水平的 IGF-II和组织蛋白酶D在AA乳腺癌患者的配对组织中存在，它们的表达 与存活率下降有关。我们将在体外和体内进一步测试我们的假设。黄连素的体外分析 从再生障碍性贫血患者建立的乳腺癌细胞将使我们能够识别特定形式的IGF-II和 这些细胞分泌的CD与高加索患者细胞分泌的CD相比较。更高 IGF-II和CD的分子形式与糖基化有关，对肿瘤的促进作用更强 进步。体内动物模型将使我们能够描述疾病的发展过程。 CD、IGF-II和EFABP与疾病进展的相关性将提供急需的洞察力 了解这些因素的不同表达如何解释差异的机制 在AA乳腺癌患者中观察的生存结果。技术目标、研究设计和 这项提案的方法将确认、扩展和扩展这些初步发现。假设将是 如果实现了这些技术目标，则提供支持。

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.