Regulation of angiogenesis and tumorigenesis by signal transduction cascades: lessons from benign and malignant endothelial tumors.
Regulation of angiogenesis and tumorigenesis by signal transduction cascades: lessons from benign and malignant endothelial tumors.
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通过信号转导级联调节血管生成和肿瘤发生：良性和恶性内皮肿瘤的教训。
DOI：
10.1046/j.1087-0024.2000.00007.x
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Arbiser,JL
中科院分区：
文献类型：
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作者：
Klafter,R;Arbiser,JL
癌基因和肿瘤抑制基因参与血管生成开关的调节。迄今为止积累的大部分数据使用NIH 3 T3细胞作为这些研究的模型，NIH 3 T3细胞缺乏肿瘤抑制基因p16。我们已经使用了一种新的系统，通过顺序引入一个温度敏感的SV 40大T抗原和致癌H-ras，研究血管生成开关。我们的研究结果与使用NIH 3 T3细胞的结果不同，但已被多个其他小组证实。来自所有这些研究的数据表明，p53肿瘤抑制基因的失活和磷酸肌醇-3-激酶途径（PI-3-K）的激活之间存在协同作用，以及p16肿瘤抑制基因的失活和MAP激酶途径的激活之间存在协同作用。这些研究结果表明，有可预测的肿瘤行为，可以通过活检中p53或p16的状态进行评估，并且这些可预测的信号转导变化可能在诊断学上和良性和恶性肿瘤的合理药物治疗设计中都是有用的。
Oncogenes and tumor suppressor genes are implicated in the regulation of the angiogenic switch. Much of the data accumulated to date uses NIH 3T3 cells, which are deficient in the tumor suppressor gene p16, as models for these studies. We have used a novel system, derived by sequential introduction of a temperature-sensitive SV40 large T antigen and oncogenic H-ras, to study the angiogenic switch. The results from our studies differ from those using NIH3T3 cells, but have been confirmed by multiple other groups. The data from all of these studies suggest that there is synergy between inactivation of the p53 tumor suppressor gene and activation of the phosphoinositol-3-kinase pathway (PI-3-K), as well as synergy between inactivation of the p16 tumor suppressor gene and activation of the MAP kinase pathway. These findings suggest that there are predictable behaviors of tumors that may be assessed by the status of p53 or p16 in a biopsy, and that these predictable changes in signal transduction may be useful both prognostically and in the design of rationally based drug therapy of benign and malignant tumors.