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。的目的 研究建议是确定阳性血管生成因子的作用， 称为血管内皮生长因子（VEGF）及其辅助受体 神经纤毛蛋白-1（NRP-1）的细胞和分子序列的事件， 雌激素在大鼠垂体中产生肿瘤血管生成。四个具体目标 概述了在三年内实现这一目标的目标。具体 目的1将阐明雌激素对VEGF 164表达的影响， NRP-1在不同品系大鼠及其杂种F1垂体中的表达 通过分析基因和蛋白质产物来获得后代。具体目标2： 雌激素与VEGF 164和NRP-1相互作用的机制 将在转录水平上进行检查。第三个目标将阐明 NRP-1在催乳素分泌型垂体瘤细胞中的过度表达， 细胞存活和血管生成。具体目标4将解决以下问题： 影响VEGF 164作用的负调节因子如血小板反应蛋白-1 在雌激素诱导的肿瘤血管生成的发展过程中， 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.