ROLE OF VEGF AND NRP 1 IN ESTROGEN INDUCED ANGIOGENESIS

血管内皮细胞的增殖是早期和 促进细胞生长的血管生成的关键步骤。这样做的目的是 研究建议是确定正向血管生成因子的作用， 血管内皮细胞生长因子及其辅受体 神经粘连蛋白-1(NRP-1)在细胞和分子序列中的作用 雌激素在大鼠脑下垂体产生肿瘤血管生成。四个具体目标 计划在三年内实现这一目标。特定的 目的1阐明雌激素对血管内皮细胞生长因子164和 不同品系大鼠及其杂交F1脑垂体中NRP-1的表达 通过分析基因和蛋白质产物产生后代。在具体目标2中 雌激素与VEGF164和NRP-1相互作用的机制 在转录层面上将进行审查。第三个目的将阐明 NRP-1在分泌催乳素的垂体瘤细胞中的过度表达及其作用 细胞存活和血管生成。具体目标4将解决以下问题： 影响血管内皮生长因子164作用的负性调节因子如凝血酶反应蛋白-1 在雌激素诱导的肿瘤血管生成过程中， NRP-1的表达。

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.