p53-dependent regulation of VEGF expression and activity

VEGF 表达和活性的 p53 依赖性调节

• 批准号: 6837088
• 负责人: MARK W. JACKSON
• 金额: $ 5.15万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837088
• 关键词: angiogenesis; biological signal transduction; cell proliferation; cell surface receptors; connective tissue growth factor; fatty acid binding protein; metastasis; neoplastic transformation; northern blottings; p53 gene /protein; plasmids; postdoctoral investigator; protein binding; protein protein interaction; protein structure function; tissue /cell culture; transfection /expression vector; vascular endothelial growth factors; western blottings

DESCRIPTION (provided by applicant): The observation that p53 mutation is strongly correlated with VEGF expression and increased vascular density demonstrates the significance of understanding the mechanisms utilized by p53 to control angiogenesis. Towards deciphering the role of p53 in regulating angiogenesis, three genes identified by gene array technology as p53- regulated have been chosen for further examination. Cutaneous fatty acid binding protein (cFABP), connective tissue growth factor (CTGF) and endothelial and smooth muscle cell-derived neuropilin-like molecule (ESDN) are regulated in a p53-dependent manner following induction by pl4ARF. The interest in each lies with their ability to alter VEGF expression or activity. The expression of cFABP, CTGF or ESDN has not previously been linked to p53 expression, an observation that may provide insight into the regulation of VEGF activities by p53. Given these observations, the focus of this proposed study is to decipher the roles, either separately or collectively, of cFABP, CTGF and ESDN in the regulation of YEGF-mediated tumor angiogenesis and metastasis. The findings of this study will allow a more thorough understanding of p53-mediated signaling in tumor angiogenesis and invasion.

描述（由申请人提供）：p53突变与VEGF表达和血管密度增加密切相关的观察结果证明了理解p53控制血管生成的机制的重要性。为了解释p53在调节血管生成中的作用，选择了通过基因阵列技术鉴定为p53调节的三个基因进行进一步检查。皮肤脂肪酸结合蛋白（cFABP）、结缔组织生长因子（CTGF）以及内皮和平滑肌细胞衍生的神经纤毛蛋白样分子（ESDN）在p14ARF诱导后以p53依赖性方式调节。对每一种的兴趣在于它们改变VEGF表达或活性的能力。cFABP、CTGF或ESDN的表达以前未与p53表达相关联，这一观察结果可提供对p53调节VEGF活性的深入了解。 鉴于这些观察结果，本研究的重点是分别或共同解读cFABP、CTGF和ESDN在YEGF介导的肿瘤血管生成和转移调节中的作用。本研究的发现将使我们更深入地了解p53介导的信号在肿瘤血管生成和侵袭中的作用。