Targeting gene expression to hypoxic tumor cells
Targeting gene expression to hypoxic tumor cells
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DOI：
10.1038/nm0597-515
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发表时间：
1997-05-01
期刊：
影响因子：
82.9
通讯作者：
Harris, AL
中科院分区：
文献类型：
--
作者：
Dachs, GU;Patterson, AV;Harris, AL
具有低氧张力（缺氧）区域的实体瘤预后较差，因为这种环境中的细胞通常能在放射和化疗中存活下来。在本报告中，我们描述了如何利用这种缺氧环境来激活由缺氧反应元件（HRE）驱动的异源基因表达，该元件与转录复合物缺氧诱导因子-1（HIF-1）相互作用。我们的结果表明，HIF-1/HRE 基因调控系统在缺氧肿瘤细胞中活跃，并显示出在癌症治疗中利用肿瘤特异性条件来靶向表达诊断或治疗基因的潜力。
Solid tumors with areas of low oxygen tension (hypoxia) have a poor prognosis, as cells in this environment often survive radiation and chemotherapy. In this report we describe how this hypoxic environment can be used to activate heterologous gene expression driven by a hypoxia-responsive element (HRE), which interacts with the transcriptional complex hypoxia-inducible factor-1 (HIF-1). Our results demonstrate that the HIF-1/HRE system of gene regulation is active in hypoxic tumor cells and show the potential of exploiting tumor-specific conditions for the targeted expression of diagnostic or therapeutic genes in cancer therapy.