Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers.
Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers.
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DOI：
10.1186/1471-2156-5-27
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发表时间：
2004-09-02
期刊：
影响因子：
2.9
通讯作者：
Cangul H
中科院分区：
文献类型：
--
作者：
Cangul H
NDRG 1基因的表达是由镍诱导的，镍是一种与钴具有相似物理性质的过渡金属。镍可以在细胞中产生缺氧样条件并诱导缺氧反应基因，钴也是如此。NDRG 1可能是另一个缺氧诱导的基因。HIF-1是一种在缺氧反应基因调控中起重要作用的转录因子，可能参与NDRG 1基因的转录调控。缺氧是实体瘤的常见特征，因此研究Ndrg 1蛋白在人类癌症中的表达是有意义的。缺氧及其模拟物诱导NDRG 1基因在体外表达并引起NDRG 1蛋白的积累。即使细胞恢复到常氧状态，蛋白质水平仍然很高。虽然HIF-1参与NDRG 1的调节，但在HIF-1敲除细胞中，长期缺氧在一定程度上诱导该基因。在研究的大多数人体组织中，与正常组织相比，Ndrg 1蛋白在癌症中过表达，并且也比HIF-1蛋白更好地反映肿瘤缺氧。缺氧是NDRG 1基因的诱导剂，镍可能通过与氧感觉通路相互作用而引起该基因的诱导。NDRG 1的低氧诱导主要依赖于HIF-1转录因子，但在慢性低氧期间，该基因的调节也涉及HIF-1非依赖性途径。Ndrg 1蛋白在癌症中的水平测定可能有助于疾病的诊断。
The expression of NDRG1 gene is induced by nickel, a transition metal sharing similar physical properties to cobalt. Nickel may create hypoxia-like conditions in cells and induce hypoxia-responsive genes, as does cobalt. Therefore NDRG1 is likely to be another gene induced by hypoxia. HIF-1 is a transcription factor which has a major role in the regulation of hypoxia-responsive genes, and thus it could be involved in the transcriptional regulation of NDRG1 gene. Hypoxia is such a common feature of solid tumours that it is of interest to investigate the expression of Ndrg1 protein in human cancers. Hypoxia and its mimetics induce in vitro expression of NDRG1 gene and cause the accumulation of Ndrg1 protein. Protein levels remain high even after cells revert to normoxia. Although HIF-1 is involved in the regulation of NDRG1, long term hypoxia induces the gene to some extent in HIF-1 knock-out cells. In the majority of human tissues studied, Ndrg1 protein is overexpressed in cancers compared to normal tissues and also reflects tumour hypoxia better than HIF-1 protein. Hypoxia is an inducer of the NDRG1 gene, and nickel probably causes the induction of the gene by interacting with the oxygen sensory pathway. Hypoxic induction of NDRG1 is mostly dependent on the HIF-1 transcription factor, but HIF-1 independent pathways are also involved in the regulation of the gene during chronic hypoxia. The determination of Ndrg1 protein levels in cancers may aid the diagnosis of the disease.
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