Functional Analysis of TEM5 and TEM8

TEM5和TEM8的功能分析

• 批准号: 7292195
• 负责人: Bradley D St Croix
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7292195
• 关键词: Functional; Analysis; TEM5; TEM8; Functional; Analysis; TEM5; TEM8

Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes upregulated in endothelial cells that line tumor blood vessels, called Tumor endothelial markers (TEMs). Two of these, TEM5 and TEM8 are of particular interest because they reside on the cell surface and may therefore be directly accessible to blood-borne therapeutics. In an attempt to understand the functional role of TEM5 and TEM8 in angiogenesis, we have begun to generate TEM5 and TEM8 gene knockouts. Because these genes are also likely to be involved developmental angiogenesis we are generating conditional floxed alleles using cre/flp technology such that the gene can be disrupted specifically in adult tissues. By challenging gene disrupted mice with tumors, we hope to determine if either of these genes is critical for tumor angiogenesis. The studies should also allow us to better understand the function of these genes in angiogenesis.

肿瘤取决于新的血管形成或血管生成，以进行广泛的生长。我们最近对基因表达的分析导致对肿瘤血管（称为肿瘤内皮标记物（TEMS））的内皮细胞中上调的几个基因的鉴定。其中两个，TEM5和TEM8特别关注，因为它们驻留在细胞表面，因此可以直接被血源性治疗。为了了解TEM5和TEM8在血管生成中的功能作用，我们开始生成TEM5和TEM8基因敲除。由于这些基因也可能涉及发育血管生成，因此我们使用CRE/FLP技术产生条件性的flox等位基因，以便可以在成人组织中专门破坏该基因。通过挑战基因用肿瘤破坏小鼠，我们希望确定这些基因中的任何一种对于肿瘤血管生成至关重要。这些研究还应该使我们能够更好地理解这些基因在血管生成中的功能。