低氧诱导因子在肾透明细胞癌中作用的研究进展  

Research Progress of the Role of Hypoxia-inducible Factor in Renal Cell Carcinoma

作　　者：项鹏程 孙鹏程[1] 刘玉伟[1] 卢云汉[1] 徐万海[1] XIANG Peng-cheng SUN Peng-cheng LIU Yu-wei LU Yun-han XU Wan-hai(The fourth hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, China)

机构地区：[1]哈尔滨医科大学附属第四医院,黑龙江哈尔滨150001

出　　处：《现代生物医学进展》2017年第10期1975-1980,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年科学基金项目(30900354)

摘　　要：VHL基因具有调节转录、稳定细胞生长相关基因和调节细胞周期的功能,其突变、缺失、重排和超甲基化与肾细胞癌(RCC)的发生密切相关。VHL基因产物VHL肿瘤抑制蛋白(p VHL)是泛素连接酶的成分,具有调节低氧诱导因子(HIF)稳定性的作用。HIF家族主要包含三种HIFα因子(HIF1α、HIF2α、HIF3α)和两种HIFβ因子(HIF1β、HIF2β)。HIF1α位于14q染色体上,在肾透明细胞癌中该染色体经常缺失,且这种14q的缺失常伴有预后不良。HIF2α的表达异常促进了p VHL缺陷型肾透明细胞癌中的发生。目前,抑制HIF2α及其下游的血管内皮生长因子(VEGF)的药物都处于临床试验的不同阶段,已有四种VEGF抑制剂获准用于肾透明细胞癌的治疗。选择抑制HIF或具有HIF靶基因抑制选择性的药物进行研究,可能为肾透明细胞癌的治疗提供新的方法。本文就HIF在VHL蛋白缺陷型肾透明细胞癌中作用的研究进展进行了综述。VHL gene has the function of regulating transcription, stabling cell growth related gene and regulating the cell cycle, the mutations, deletions, rearrangements and hypermethylation of VHL gene are closely related with the renal cell carcinoma （RCC）. VHL gene product （pVHL） is a component of the ubiquitin ligase, which can regulate the stability of hypoxia-inducible factor （H/F）. H/F family includes three kinds of HIFcc factors （HIFlct, HIF2oc, HIF3cx） and two kinds of HIFI3 factors （HIFll3, HIF213）. HIFla is located on the chromosome 14q which is often missing in renal clear cell carcinoma and related to the poor prognosis. Abnormal expression of HIF2ct promotes the incidence of pVHL-deftcient renal cell carcinoma. Currently, the drugs which can inhibit HIF2ct and its downstream vascular endothelial growth factor（VEGF） are in various stages of clinical trials, and there are four types ofVEGF inhibitors approved for the treatment of renal cell carcinoma. So the research on the drugs that can inhibit H/F or HIF target genes may offer a new method for the treatment of renal clear cell carcinoma. In this paper, the research progress of role of H/F in pVI-IL-deficient renal cell carcinoma, is reviewed.

关 键 词：肾透明细胞癌 VHL基因 低氧诱导因子 血管内皮生长因子 

分 类 号：R730.2[医药卫生—肿瘤]