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学科主题: 临床医学
题名:
The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1 alpha and-2 alpha in sporadic clear cell renal carcinoma
作者: Gong, Kan1; Zhang, Ning2; Zhang, Kai3; Na, Yanqun1
关键词: kidney carcinoma ; renal cell ; erythropoietin ; von Hippel-Lindau mutation ; hypoxia-inducible factor
刊名: INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
发表日期: 2010-12-01
DOI: 10.3892/ijmm_00000541
卷: 26, 期:6, 页:907-912
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental
研究领域[WOS]: Research & Experimental Medicine
关键词[WOS]: GROWTH-FACTOR ; CANCER ; EXPRESSION ; PROTEIN ; COEXPRESSION ; RECEPTOR ; IDENTIFICATION ; INACTIVATION ; KIDNEY
英文摘要:

Decreased levels of von Hippel-Lindau (VHL) tumour suppressor protein are associated with up-regulation of hypoxia-inducible factor (HIF), leading to increased tumour proliferation, angiogenesis and progression. The role of erythropoietin (EPO), a target gene for HIF, remains unknown for sporadic clear cell renal cell carcinoma (sCCRCC). In this study, we determined expression levels of EPO, and its correlation with VHL mutations and HIF-1 alpha and HIF-2 alpha expression in 82 patients identified with sCCRCC following nephrectomy. We identified VHL gene alterations using multiplex polymerase chain reaction, purifying products of polymerase chain reaction, and direct sequencing. Immunohistochemical staining for HIF-1 alpha, HIF-2 alpha and EPO was performed for tumour and corresponding normal tissues. Data were analyzed with respect to clinicopathological factors. EPO was detected in 87.8% of sCCRCC tumours versus 7.3% for normal tissues. EPO expression was related to tumours demonstrating VHL gene abnormalities. Of specimens with VHL alterations 95.6% tested positive for EPO, versus 78.3% when VHL gene expression was normal (P<0.01). EPO was identified in 96.2 and 94.2% of HIF-1 alpha and HIF-2 alpha positive specimens, respectively, compared to 72.4 and 53.8% for HIF-1 alpha and HIF-2 alpha negative groups (p<0.01). Moreover, EPO expression correlated significantly with increasing nuclear grade (p<0.05). HIF-2 alpha was identified in 84.1% of sCCRCC, compared to 64.6% for HIF-1 alpha. Expression of HIF-1 alpha, HIF-2 alpha and EPO is common in sCCRCC. Although both forms of HIF up-regulate expression of EPO, the relationship to HIF-2 alpha appears to be more pronounced. The VHL-HIF-EPO pathway requires further study, as it may represent a potential molecular target for therapy of sCCRCC.

语种: 英语
WOS记录号: WOS:000285035800018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53098
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Beijing Chaoyang Hosp, Dept Urol, Beijing, Peoples R China
2.Beijing Canc Hosp, Dept Urol, Beijing, Peoples R China
3.Peking Univ, Dept Urol, Hosp 1, Inst Urol, Beijing 100034, Peoples R China

Recommended Citation:
Gong, Kan,Zhang, Ning,Zhang, Kai,et al. The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1 alpha and-2 alpha in sporadic clear cell renal carcinoma[J]. INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,2010,26(6):907-912.
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