HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity.
Cancer Cell
; 11(4): 335-47, 2007 Apr.
Article
em En
| MEDLINE
| ID: mdl-17418410
ABSTRACT
HIF-2alpha promotes von Hippel-Lindau (VHL)-deficient renal clear cell carcinoma (RCC) tumorigenesis, while HIF-1alpha inhibits RCC growth. As HIF-1alpha antagonizes c-Myc function, we hypothesized that HIF-2alpha might enhance c-Myc activity. We demonstrate here that HIF-2alpha promotes cell-cycle progression in hypoxic RCCs and multiple other cell lines. This correlates with enhanced c-Myc promoter binding, transcriptional effects on both activated and repressed target genes, and interactions with Sp1, Miz1, and Max. Finally, HIF-2alpha augments c-Myc transformation of primary mouse embryo fibroblasts (MEFs). Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Transcrição Gênica
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Hipóxia Celular
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Proteínas Proto-Oncogênicas c-myc
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Neoplasias do Colo
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Proliferação de Células
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article