p53-dependent regulation of VEGF expression and activity

描述（由申请人提供）：观察到p53突变与VEGF表达和血管密度增加密切相关，表明了解p53控制血管生成的机制具有重要意义。为了揭示p53在血管生成中的作用，我们选择了三个经基因阵列技术鉴定为p53调控的基因进行进一步的研究。在pl4ARF诱导下，皮肤脂肪酸结合蛋白（cFABP）、结缔组织生长因子（CTGF）以及内皮细胞和平滑肌细胞源性神经匹林样分子（ESDN）以p53依赖的方式调节。人们对这两种药物的兴趣在于它们改变VEGF表达或活性的能力。cFABP、CTGF或ESDN的表达与p53的表达没有关联，这一观察结果可能为p53对VEGF活性的调节提供新的思路。鉴于这些观察结果，本研究的重点是解读cFABP、CTGF和ESDN在调节yegf介导的肿瘤血管生成和转移中的作用，无论是单独的还是共同的。本研究的发现将使我们对p53介导的信号在肿瘤血管生成和侵袭中的作用有更深入的了解。

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.