Angiogenesis in Breast Cancer

描述(申请人提供)：本申请集中于一种重要的内皮细胞酪氨酸激酶受体Tie-2及其下游效应器。Tie-2对胚胎发育至关重要，空胚胎无法正确组装血管。最近的研究表明，阻断Tie-2配体结合会损害肿瘤血管生成。我们提供的初步数据表明，该受体的激酶功能对肿瘤血管生成至关重要，可能介导这一功能的下游途径包括Akt信号和凝血酶反应蛋白的表达。这项应用的目的是进一步探索Tie-2激酶活性及其下游效应因子和乳腺肿瘤血管形成之间的关系。 目的1：探讨Tie-2蛋白在乳腺肿瘤及转移瘤血管生成和血管生成中的作用。 目的：研究凝血酶敏感蛋白、Akt信号转导或两者共同作用是否介导Tie-2调控乳腺肿瘤血管生成或血管生成。

DESCRIPTION (provided by applicant): This application focuses on an important endothelial cell tyrosine kinase receptor, Tie-2 and its downstream effectors. Tie-2 is essential for embryonic development and null embryos fail to properly assemble blood vessels. Recent investigations show that blocking Tie-2 ligand binding impairs tumor angiogenesis. We show preliminary data to suggest that the kinase function of this receptor is critical for tumor angiogenesis and that downstream pathways that may mediate this function include Akt signaling and thrombospondin expression. The goal of this application is to further explore the relationship between the Tie-2 kinase activity, its downstream effectors, and mammary tumor vascularization. Aim 1: Determine the function of Tie-2 kinase function in the angiogenesis and vasculogenesis of mammary tumors and metastases. Aim 2: Investigate whether Thrombospondins, Akt signaling, or both, mediate Tie-2 regulation of mammary tumor angiogenesis or vasculogenesis.