Angiogenesis in Breast Cancer

描述（由申请人提供）：本申请侧重于一种重要的内皮细胞酪氨酸激酶受体Tie-2及其下游效应物。Tie-2对胚胎发育至关重要，而无胚不能正常组装血管。最近的研究表明，阻断Tie-2配体结合会损害肿瘤血管生成。我们显示的初步数据表明，该受体的激酶功能对肿瘤血管生成至关重要，下游通路可能介导该功能，包括Akt信号传导和血栓反应蛋白的表达。本申请的目的是进一步探讨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。

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.