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血管内皮生长因子基因的转录调控——激活因子的协同作用

Transcriptional regulation of the Vascular Endothelial Growth Factor gene--a concert of activating factors.

作者信息

Pagès Gilles, Pouysségur Jacques

机构信息

Institute of Signaling, Developmental Biology and Cancer Research, CNRS-UMR 6543, Centre Antoine Lacassagne, 33 avenue de Valombrose, 06189 Nice cedex 2, France.

出版信息

Cardiovasc Res. 2005 Feb 15;65(3):564-73. doi: 10.1016/j.cardiores.2004.09.032.

Abstract

The vascular endothelial growth factor A (VEGF-A) is essential during embryonic development as inactivation of only one allele of its gene results in embryonic lethality. Up-regulation of VEGF under physiological situations allows for adaptation to hypoxic stress, to transient inflammatory processes, and to wounding. Its expression also increases all along the process of neovascularization of solid and hematological tumors. The object of this article is to focus on the transcriptional regulation of its gene. The major cis-acting sequences and trans-activating factors will be described as well as the physiological and pathological situations leading to the intervention of such sequences and factors. We will also focus on two transcription factors essential to VEGF gene transcription: the hypoxia-inducible factor-1, which is responsible for its increased by hypoxia, as well as Sp1, which is implicated in the response to various extracellular stimuli.

摘要

血管内皮生长因子A(VEGF-A)在胚胎发育过程中至关重要,因为其基因仅一个等位基因失活就会导致胚胎致死。在生理情况下VEGF的上调可使机体适应低氧应激、短暂性炎症过程和创伤。在实体瘤和血液肿瘤的整个新血管形成过程中,其表达也会增加。本文的目的是聚焦于其基因的转录调控。将描述主要的顺式作用序列和反式激活因子,以及导致此类序列和因子发挥作用的生理和病理情况。我们还将聚焦于VEGF基因转录所必需的两个转录因子:负责其在低氧情况下表达增加的低氧诱导因子-1,以及参与对各种细胞外刺激作出反应的Sp1。

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