田立志 沈阳 项鹏程 许涛 王晓民 高琳 徐万海.缺氧诱导因子与肾细胞癌关系的研究进展[J].,2015,15(1):188-190 |
缺氧诱导因子与肾细胞癌关系的研究进展 |
The Research on Hypoxia Inducible Factor and Renal Cell Cancer |
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DOI: |
中文关键词: 缺氧诱导因子因子 肾细胞癌 血管生成 缺氧反应基因 |
英文关键词: Hypoxia inducible factor Renal cell cancer Angiogenesis Hypoxia response gene |
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中文摘要: |
缺氧诱导因子(hypoxia inducible factor,HIF) 对维持肿瘤细胞的能量代谢、肿瘤血管生成、促进肿瘤细胞增殖和转移起着重
要作用,是肿瘤细胞低氧条件下产生的关键信号分子。本综述旨在总结前人研究,阐述HIF与肾癌细胞之间的内在关系。HIF成员是参与肾癌细胞对缺氧应答反应中的关键因子,并通过靶基因的调节,促进新生血管的生成,导致肿瘤生长。其中,HIF-1alpha及HIF-2alpha在促进新生血管的生成方面发挥着主要作用。HIF-1alpha及HIF-2alpha与VEGF密切相关,随着其的表达增高,VEGF在数量上及mRNA 水平上均显著增高,显示其可通过调控VEGF 参与肾癌血管生成,而HIF-2alpha转录激活VEGF mRNA 的特异性较HIF-1alpha更强。HIF-3alpha可能存在的负性调控作用,其异构体-4 的作用可能与HIF-lalpha的负性调节有关,其可以阻止HIF-lalpha与下游靶基因的缺氧反应元件(hypoxia response elements,HRE)结合,同时可在转录水平抑制HIF-l琢。HIF在未来可能有成为肾细胞癌治疗
的靶点。 |
英文摘要: |
Hypoxia inducible factor (HIF) played an important role to maintain the energy metabolism of tumor cells, tumor angiogenesis,
proliferation and metastasis of tumor cells, which was the key signal molecule in the tumor cells hypoxia. This review aimed
to summarize previous research, elaborated the intrinsic relationship between HIF and renal cancer cell. Research showed that HIF members
were involved in renal cancer cell on the key factor in the hypoxia response, which could promote angiogenesis and tumor growth
through the regulation of target genes. Among them, HIF-1alpha and HIF-2alpha played an important role in promoting the formation of new
blood vessels. HIF-1alpha and HIF-2alpha was highly correlated with VEGF, and VEGF and mRNA levels significantly increased with its expression increased in number, which showed participation in renal cell cancer angiogenesis through the regulation of VEGF. While the
specificity of activating transcription of VEGF mRNA by HIF-2alpha stronger than that by HIF-1alpha. But HIF-3alpha played negative regulation
role, the negative regulation of -4 isomers might be related to HIF-lalpha , which prevented HIF-lalpha binding with the downstream target genes
of hypoxia response elements (HRE), also at the level of transcription. HIF has become a renal cell cancer targeting new treatment target
in the future. |
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