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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >p53-mediated inhibition of angiogenesis in diffuse low-grade astrocytomas.
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p53-mediated inhibition of angiogenesis in diffuse low-grade astrocytomas.

机译：p53介导的弥漫性低度星形细胞瘤中血管生成的抑制。

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摘要

The p53 tumour suppressor protein has long been recognized as the central factor protecting humans from cancer. In this study we evaluated the associations of p53 status and vessel density (angiogenesis) in a set of diffuse low-grade astrocytomas. Immunohistochemistry was performed on 23 diffuse low-grade astrocytomas for CD31 and p53. Mutations in the TP53 gene were identified by PCR amplification of genomic DNA extracted from the indicated tumour tissues. Microvessel counts were done by computer analyses. Intratumoural or peritumoural microvascular hot spots were assessed and analysed from an image taken with a 200x fold magnification. Statistical analysis was performed with Pearson correlation coefficient and Student's t-test. We found that 9/23 (39%) of the astrocytomas stained positive for p53 in the immunohistochemistry. We identified TP53 mutations in 11/23 (47%) of the astrocytomas. No association between micro vessel density (MVD) and p53 immunohistochemical status was found. However, the MVD was significantly increased in p53 mutated low-grade astrocytomas. Furthermore, the absolute vessel number was significantly higher in p53 mutated than in p53 wild-type low-grade astrocytomas. To analyse the molecular background for that epiphenomenon LN229 glioma cells which harbour a TP53 mutation were transfected with a plasmid encoding p53 wild-type and an angiogenesis protein array was performed. We detected a significant increase for thrombospondin-1, coagulation factor III and serpin E1 and a significant decrease of MMP-9 in wild-type p53 transfected LN229 cells. The higher microvessel density and the increased absolute vessel number in p53 mutated tumours supports the importance of p53 for tumour angiogenesis in diffuse low-grade astrocytomas. Our results support the hypothesis that p53 regulates angiogenesis in low-grade astrocytomas.
机译：长期以来，人们一直认为p53抑癌蛋白是保护人类免受癌症侵害的中心因素。在这项研究中，我们评估了一组弥散性低度星形细胞瘤中p53状态与血管密度（血管生成）的关系。对23种弥漫性低度星形细胞瘤进行了CD31和p53的免疫组织化学分析。通过PCR扩增从指示的肿瘤组织中提取的基因组DNA来鉴定TP53基因中的突变。微血管计数通过计算机分析进行。从放大200倍的图像中评估并分析了瘤内或瘤周围微血管热点。使用Pearson相关系数和Student t检验进行统计分析。我们发现，在免疫组织化学中9/23（39％）的星形细胞瘤对p53染色呈阳性。我们在星形细胞瘤的11/23（47％）中发现了TP53突变。没有发现微血管密度（MVD）和p53免疫组化状态之间的关联。但是，MVD在p53突变的低度星形细胞瘤中显着增加。此外，p53突变的绝对血管数明显高于p53野生型低度星形细胞瘤。为了分析该现象的分子背景，用编码p53野生型的质粒转染带有TP53突变的LN229神经胶质瘤细胞，并进行血管生成蛋白阵列。我们在野生型p53转染的LN229细胞中检测到血小板反应蛋白1，凝血因子III和丝氨酸蛋白酶抑制剂E1显着增加，而MMP-9显着降低。 p53突变的肿瘤中较高的微血管密度和绝对的血管数增加，支持了p53对弥漫性低度星形细胞瘤中肿瘤血管生成的重要性。我们的结果支持p53调节低度星形细胞瘤血管生成的假设。

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