Expression of hypoxia inducible factor-1alpha and 2alpha in genetically distinct early renal cortical tumors.
J Urol
; 175(5): 1908-14, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16600797
ABSTRACT
PURPOSE:
The role of the HIF class of transcription factors has been implicated to be a critical step in clear cell kidney tumorigenesis. To assess if HIF over expression is a prominent feature of other renal cell carcinoma histological subtypes we characterized the expression of HIF-1alpha and HIF-2alpha in genetically distinct early renal cortical tumors. MATERIALS ANDMETHODS:
Nascent renal tumors of distinct histology from patients with a hereditary renal tumor syndrome were characterized for HIF expression using high amplification immunohistochemistry. In addition, indirect immunofluorescence and confocal microscopy were used for subcellular localization of HIF-1alpha and 2alpha in clear cell renal carcinoma cells.RESULTS:
Clear cell RCC tumors from patients with von Hippel-Lindau disease strongly expressed HIF-1alpha and HIF-2alpha (10 of 12 and 12 of 12 tumors, respectively). Chromophobe tumors from patients with Birt-Hogg-Dubé syndrome expressed predominantly HIF-2alpha with weaker HIF-1alpha expression (12 of 12 and 6 of 12 tumors, respectively). Consistent HIF-1alpha expression was not seen in type I papillary tumors from patients with hereditary papillary renal carcinoma (3 of 12 tumors). However, half of the type I papillary tumors (6 of 12) expressed HIF-2alpha.CONCLUSIONS:
Differential patterns of HIF-1alpha and HIF-2alpha protein over expression were found among the 3 human kidney tumor types associated with multifocal hereditary kidney tumor syndromes. Consistent, simultaneous over expression of HIF-1alpha and HIF-2alpha appears to be specific to VHL negative clear cell renal cell carcinoma. Consistent HIF-2alpha expression was found in all 3 renal cortical tumor subtypes, suggesting a pivotal role in renal cortical tumorigenesis. Differential function of HIF-1alpha vs HIF-2alpha is suggested by the distinct subcellular localization pattern of HIF-1alpha and HIF-2alpha in clear cell renal carcinoma cells.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Carcinoma de Células Renais
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Regulação Neoplásica da Expressão Gênica
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Córtex Renal
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Neoplasias Renais
Limite:
Humans
Idioma:
En
Revista:
J Urol
Ano de publicação:
2006
Tipo de documento:
Article