Angiogenesis in Breast Cancer

乳腺癌中的血管生成

• 批准号: 7001312
• 负责人: LAURA E BENJAMIN
• 金额: $ 32.79万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7001312
• 关键词: angiogenesis; biological signal transduction; breast neoplasms; disease /disorder model; enzyme activity; enzyme inhibitors; genetic manipulation; genetically modified animals; laboratory mouse; metastasis; neoplasm /cancer blood supply; neoplastic process; protein tyrosine kinase; protooncogene; receptor binding; receptor expression; thrombospondins

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.

描述（由申请人提供）：此申请专注于重要的内皮细胞酪氨酸激酶受体，TIE-2及其下游效应子。 TIE-2对于胚胎发育至关重要，无效的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。 我们显示了初步数据，以表明该受体的激酶功能对于肿瘤血管生成至关重要，并且可能介导此功能的下游途径包括AKT信号传导和血小板传播表达。 该应用的目的是进一步探索TIE-2激酶活性，其下游效应子和乳腺肿瘤血管形成之间的关系。 目标1：确定TIE-2激酶功能在乳腺肿瘤和转移酶的血管生成和血管生成中的功能。 目标2：研究血小板蛋白，AKT信号传导或两者是否介导TIE-2调节乳腺肿瘤血管生成或血管生成。