Angiogenesis in Breast Cancer

描述（由申请人提供）：本申请关注一种重要的内皮细胞酪氨酸激酶受体Tie-2及其下游效应物。 Tie-2对胚胎发育至关重要，无效胚胎无法正确组装血管。 最近的研究表明，阻断Tie-2配体结合损害肿瘤血管生成。 我们显示的初步数据表明，这种受体的激酶功能是至关重要的肿瘤血管生成和下游途径，可能介导这种功能，包括Akt信号和血小板反应蛋白的表达。 本申请的目的是进一步探索Tie-2激酶活性及其下游效应物与乳腺肿瘤血管化之间的关系。 目的1：研究Tie-2激酶在乳腺肿瘤血管生成和转移中的作用。 目的2：研究是否凝血酶敏感蛋白，Akt信号，或两者，介导Tie-2调节乳腺肿瘤血管生成或血管发生。

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.