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

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-1α及HIF-2α在促进新生血管的生成方面发挥着主要作用。HIF-1α及HIF-2α与VEGF密切相关,随着其的表达增高,VEGF在数量上及m RNA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-2α转录激活VEGF m RNA的特异性较HIF-1α更强。HIF-3α可能存在的负性调控作用,其异构体-4的作用可能与HIF-lα的负性调节有关,其可以阻止HIF-lα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-lα。HIF在未来可能有成为肾细胞癌治疗的靶点。

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-1α and HIF-2α played an important role in promoting the formation of new blood vessels. HIF-1α and HIF-2α was highly correlated with VEGF, and VEGF and m RNA 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 m RNA by HIF-2α stronger than that by HIF-1α. But HIF-3α played negative regulation role, the negative regulation of-4 isomers might be related to HIF-lα, which prevented HIF-lα 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.