p53-dependent regulation of VEGF expression and activity

描述(由申请人提供)：观察到P53突变与血管内皮生长因子的表达和血管密度增加密切相关，这表明了解P53用于控制血管生成的机制具有重要意义。为了破译P53在调节血管生成中的作用，选择了三个被基因阵列技术鉴定为P53调节的基因进行进一步的检测。经p4ARF诱导后，皮肤脂肪酸结合蛋白(CFABP)、结缔组织生长因子(CTGF)、内皮细胞和血管内皮细胞衍生的神经粘连素样分子(ESDN)以P53依赖的方式被调节。对每一种的兴趣在于它们改变血管内皮生长因子表达或活性的能力。CFABP、CTGF或ESDN的表达与P53的表达没有关联，这一观察结果可能有助于深入了解P53对VEGF活性的调节。鉴于这些观察，本研究的重点是分别或共同破译cFABP、CTGF和ESDN在YEGF介导的肿瘤血管生成和转移调控中的作用。这项研究的发现将有助于更深入地了解P53介导的信号在肿瘤血管生成和侵袭中的作用。

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.