CONTROL OF ANGIOGENESIS IN FIBROBLASTS BY P53 REGULATION OF THROMBOSPONDIN-1
CONTROL OF ANGIOGENESIS IN FIBROBLASTS BY P53 REGULATION OF THROMBOSPONDIN-1
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DOI：
10.1126/science.7521539
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发表时间：
1994-09-09
期刊：
影响因子：
56.9
通讯作者：
BOUCK, N
中科院分区：
文献类型：
--
作者：
DAMERON, KM;VOLPERT, OV;BOUCK, N
当正常细胞向恶性发展时，它们必须转变为血管生成表型，以吸引它们生长所依赖的滋养血管。在培养的成纤维细胞从李-Fraumeni患者，这种开关被发现符合野生型等位基因的p53肿瘤抑制基因的损失，是血小板反应蛋白-1（TSP-1），一种有效的抑制血管生成的表达减少的结果。转染实验表明，p53可以刺激内源性TSP-1基因，并积极调节TSP-1启动子序列。这些数据表明，在成纤维细胞中，野生型p53通过调节TSP-1的合成来抑制血管生成。
As normal cells progress toward malignancy, they must switch to an angiogenic phenotype to attract the nourishing vasculature that they depend on for their growth. In cultured fibroblasts from Li-Fraumeni patients, this switch was found to coincide with loss of the wild-type allele of the p53 tumor suppressor gene and to be the result of reduced expression of thrombospondin-1 (TSP-1), a potent inhibitor of angiogenesis. Transfection assays revealed that p53 can stimulate the endogenous TSP-1 gene and positively regulate TSP-1 promoter sequences. These data indicate that, in fibroblasts, wild-type p53 inhibits angiogenesis through regulation of TSP-1 synthesis.