ROLE OF VEGF AND NRP 1 IN ESTROGEN INDUCED ANGIOGENESIS

VEGF 和 NRP 1 在雌激素诱导的血管生成中的作用

• 批准号: 6189728
• 负责人: Sushanta K. Banerjee
• 金额: $ 17.01万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6189728
• 关键词: angiogenesis; estrogens; hormone regulation /control mechanism; laboratory rat; nerve /myelin protein; pituitary neoplasms; vascular endothelial growth factors

Proliferation of the vascular endothelium is one of the early and critical steps of angiogenesis encouraging cellular growth. The aim of this research proposal is to define the roles of the positive angiogenic factor, called the vascular endothelial growth factor (VEGF) and its co-receptor neuropilin-1 (NRP-1) in the cellular and molecular sequence of events by which estrogens produce tumor angiogenesis in the rat pituitary. Four specific aims are outlined to attain this objective over a period of three years. Specific aim 1 will elucidate the impact of estrogens on the expression of VEGF164 and NRP-1 in the pituitaries of different strains of rats and their F1 hybrid progenies by analyzing the genes and protein products. In specific aim 2 the mechanisms involved in the interaction between estrogen and VEGF164 and NRP-1 at the transcriptional level will be examined. The third aimwill elucidate the role of NRP-1, over expressed in prolactin secreting pituitary tumor cells, on cell survival and angiogenesis. Specific aim 4will address the question whether negative regulators like thrombospondin-1 that influence the action of VEGF164 during the development of estrogen induced tumor angiogenesis control the expression of NRP-1.

血管内皮的扩散是早期和 血管生成的关键步骤鼓励细胞生长。这个目的 研究建议是定义阳性血管生成因子的作用， 称为血管内皮生长因子（VEGF）及其共受体 在事件的细胞和分子序列中，Neuropilin-1（NRP-1）通过其序列 雌激素在大鼠垂体中产生肿瘤血管生成。四个具体目标 概述以在三年内实现这一目标。具体的 AIM 1将阐明雌激素对VEGF164和 不同菌株大鼠及其F1杂种的垂体中的NRP-1 通过分析基因和蛋白质产物的后代。在特定目标2中 雌激素与VEGF164和NRP-1之间相互作用涉及的机制 在转录级别将进行检查。第三个目标将阐明 NRP-1的作用，在催乳素分泌的垂体肿瘤细胞中过度表达，在 细胞存活和血管生成。特定目标4将解决这个问题是否 负调节剂（例如凝血蛋白-1）影响VEGF164的作用 在雌激素诱导的肿瘤血管生成控制过程中 NRP-1的表达。