Vandenbunder B, Wernert N, Stehelin D
Laboratoire d'Oncologie Moléculaire, CNRS URA 1160, Institut Pasteur de Lille.
Arch Inst Pasteur Tunis. 1994 Jul-Oct;71(3-4):493-509.
Does the c-ets 1 protooncogene take part in the regulation of tumor angiogenesis? The formation of new blood vessels is an essential process in embryonic development and wound healing, for tumor growth and metastasis. In situ hybridization studies have revealed that the protooncogene c-ets 1 is expressed in endothelial cells at the beginning of blood vessel formation, in normal and pathological conditions. C-ets 1 encodes a transcription factor, a protein which binds specifically to DNA and which regulates the transcription of genes containing these specific binding sequences in their promotors. Thus in vitro experiments suggest that c-ets 1 may activate the transcription of genes encoding collagenase 1, stromelysine 1 and urokinase plasminogen activator, proteases involved in extracellular matrix degradation. A working hypothesis is that c-ets 1 takes part in regulating angiogenesis by controlling the transcription of these genes whose activity is necessary for the migration of endothelial cells from preexisting capillaries. This hypothesis is discussed with respect to current experimental evidences and to the complexity of the regulatory network controlling gene transcription and extracellular matrix degradation.
原癌基因c-ets 1是否参与肿瘤血管生成的调控?新血管的形成在胚胎发育和伤口愈合过程中是一个必不可少的过程,对于肿瘤的生长和转移也是如此。原位杂交研究表明,在正常和病理条件下,原癌基因c-ets 1在血管形成初期的内皮细胞中表达。C-ets 1编码一种转录因子,一种能特异性结合DNA的蛋白质,它能调节启动子中含有这些特异性结合序列的基因的转录。因此,体外实验表明,c-ets 1可能激活编码胶原酶1、基质溶解素1和尿激酶型纤溶酶原激活剂的基因的转录,这些蛋白酶参与细胞外基质的降解。一个可行的假说是,c-ets 1通过控制这些基因的转录来参与调节血管生成,这些基因的活性对于内皮细胞从现有毛细血管迁移是必需的。结合当前的实验证据以及控制基因转录和细胞外基质降解的调控网络的复杂性,对这一假说进行了讨论。