Repression of vascular endothelial growth factor expression by the zinc finger transcription factor ZNF24
Repression of vascular endothelial growth factor expression by the zinc finger transcription factor ZNF24
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DOI：
10.1158/0008-5472.can-07-1617
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发表时间：
2007-09-15
期刊：
影响因子：
11.2
通讯作者：
Moses, Marsha A.
中科院分区：
文献类型：
--
作者：
Harper, Jav;Yan, Li;Moses, Marsha A.
血管内皮生长因子（VEGF）是一种有效的血管生成刺激因子。虽然已经鉴定了许多VEGF的正调控因子，但关于VEGF表达的负调控知之甚少。我们鉴定了一个锌指转录因子ZNF 24，它可能抑制VEGF的转录。在一系列独立的研究中观察到VEGF和ZNF 24的表达之间呈负相关。ZNF 24在血管生成肿瘤结节中上调，其中VEGF表达与血管生成前结节相比显著降低。在常氧条件下培养的人乳腺癌细胞中，ZNF 24水平显著上调，而VEGF水平较低。相反，VEGF在缺氧细胞中显著增加，而ZNF 24下调。ZNF 24和VEGF之间的负相关性也观察到在70%的匹配的cDNA对的正常和恶性组织从人类结肠和乳腺活检。ZNF 24的过表达导致VEGF的显著下调，而用小干扰RNA沉默ZNF 24导致VEGF表达增加。在MDA-MB-231细胞中共转染ZNF 24和VEGF启动子荧光素酶报告基因构建体导致VEGF启动子活性显著降低。综上所述，这些数据表明，ZNF 24参与VEGF的负调控，并可能代表一种新的VEGF转录抑制因子。
Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis. Although many positive regulators of VEGF have been identified, relatively little is known regarding the negative regulation of VEGF expression. We identified a zinc finger transcription factor, ZNF24, that may repress VEGF transcription. An inverse correlation between expression of VEGF and ZNF24 was observed in a series of independent studies. ZNF24 was up-regulated in angiogenic tumor nodules where VEGF expression is significantly decreased compared with preangiogenic nodules. In human breast carcinoma cells cultured under normoxic conditions, ZNF24 levels were significantly up-regulated whereas VEGF levels were low. In contrast, VEGF was significantly increased in hypoxic cells whereas ZNF24 was down-regulated. The same inverse correlation between ZNF24 and VEGF was also observed in 70% of matched cDNA pairs of normal and malignant tissues from human colon and breast biopsies. Overexpression of ZNF24 resulted in a significant down-regulation of VEGF, whereas silencing of ZNF24 with small interfering RNA led to increased VEGF expression. Cotransfection of ZNF24 and a VEGF promoter luciferase reporter construct in MDA-MB-231 cells resulted in a significant decrease in VEGF promoter activity. Taken together, these data suggest that ZNF24 is involved in negative regulation of VEGF and may represent a novel repressor of VEGF transcription.