三磷酸腺苷酶家族蛋白2(ATAD2)基因在许多人类肿瘤中高表达，与肿瘤患者预后密切相关，但其调控肿瘤生长的机制还不甚清楚。但ATAD2能否调控肿瘤血管生成并影响肿瘤生长还未见报道。前期研究发现， 其在子宫内膜癌中的表达与血管内皮生长因子（VEGF）成正相关；ATAD2与调控VEGF表达的HIF-1α转录因子存在相互作用，因此，我们拟深入研究ATAD2对肿瘤血管的调节作用及其机制。在子宫内膜癌细胞中，过量表达和敲低ATAD2，并利用GST pull-down、免疫共沉淀、报告基因系统、ChIP等技术确定ATAD2与HIF-1α的相互作用对VEGF表达的调节作用及其分子机制，利用成管实验、裸鼠成瘤模型、临床标本等确定受ATAD2调节的子宫内膜癌细胞分泌的VEGF对血管内皮细胞增殖、血管密肿瘤生长的影响，从而揭示ATAD2调节肿瘤生长的新机制，对于了解子宫内膜癌的发病机制及诊断预后具有重要意义。

ATAD2 (ATPase family AAA domain-containing protein 2) is overexpressed in many human cancers and correlates with prognosis of cancer patients. However, the mechanisms underlying ATAD2-mediated tumor growth are largely unknown. Angiogenesis is essential for tumor growth. It is unknown if ATAD2 controls tumor angiogenesis and subsequent tumor growth. The preliminary data in our laboratory indicated that ATAD2 expression was positively correlated with the expression of VEGF (vascular endothelial growth factor) in endometrial carcinoma and that ATAD2 interacted with HIF-1α, a transcription factor involved in regulation of VEGF expression. Based on this, we will further study the potential role for ATAD2 in regulation of tumor angiogenesis as well as the underlying mechanism. In endometrial carcinoma cells, we will overexpress or knockdown ATAD2. Using GST pull-down, coimmunoprecipitation, reporter gene system, ChIP, etc., we will investigate the effect of the ATAD2- HIF-1α interaction on VEGF expression and its mechanism. Using tube formation assay, chick chorioallantoic membrane assay, tumor-bearing nude mice model, clinical samples, etc., we will determine the effects of secreted VEGF mediated by ATAD2 in endometrial carcinoma cells on vascular endothelial cell proliferation, vessel density and tumor growth. This study will identify a novel mechanism underlying ATAD2-mediated tumor growth and is of great significance to elucidate the mechanisms of endometrial carcinoma development and diagnosis prognosis.