| Autor: |
Mark R, Morris, David J, Hughes, Ya-Min, Tian, Christopher J, Ricketts, Kah Weng, Lau, Dean, Gentle, Salwati, Shuib, Pablo, Serrano-Fernandez, Jan, Lubinski, Michael S, Wiesener, Christopher W, Pugh, Farida, Latif, Peter J, Ratcliffe, Eamonn R, Maher |
| Rok vydání: |
2009 |
| Předmět: |
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| Zdroj: |
Anticancer research. 29(11) |
| ISSN: |
1791-7530 |
| Popis: |
Inactivation of the Von Hippel-Lindau (VHL) tumour suppressor gene leading to overexpression of hypoxia-inducible transcription factors (HIF)-1alpha and -2alpha is a critical event in the pathogenesis of most clear cell renal cell carcinomas (RCC). HIF-1alpha and HIF-2alpha share significant homology and regulate overlapping repertoires of hypoxia-inducible target genes but may have differing effects on RCC cell growth. Loss of HIF-1alpha expression has been described in RCC cell lines and primary tumours. Whether mutations in the alpha-subunits of HIF-1alpha and HIF-2alpha contribute to renal tumourigenesis was investigated here.Mutation analysis of the complete coding sequence of HIF-1alpha and HIF-2alpha was carried out in primary RCC (n=40).The analysis revealed a somatic HIF1A missense substitution, p.Val116Glu, in a single RCC. Functional studies demonstrated that p.Val116Glu impaired HIF-1alpha transcriptional activity. Genotyping of HIF1A variants p.Pro582Ser and p.Ala588Thr demonstrated no significant differences between RCC patients and controls.The detection of a loss-of-function HIF1A mutation in a primary RCC is consistent with HIF-1 and HIF-2 having different roles in renal tumourigenesis, However, somatic mutations of HIF1A are not frequently implicated in the pathogenesis of RCC. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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