HIF-1alpha induces MXI1 by alternate promoter usage in human neuroblastoma cells.
Exp Cell Res
; 315(11): 1924-36, 2009 Jul 01.
Article
em En
| MEDLINE
| ID: mdl-19254710
ABSTRACT
Adaptation to low oxygen conditions is essential for maintaining homeostasis and viability in oxygen-consuming multi-cellular tissues, including solid tumors. Central in these processes are the hypoxia-inducible transcription factors, HIF-1 and HIF-2, controlling genes involved in e.g. glucose metabolism and neovascularization. Tumor hypoxia and HIF expression have also been associated with a dedifferentiated phenotype and increased aggressiveness. In this report we show that the MAX interactor-1 (MXI1) gene is directly regulated by HIF proteins in neuroblastoma and breast cancer cells. HIF-binding and transactivation were detected within MXI1 gene regulatory sequences in the vicinity of the MXI1-0 promoter, leading to rapid induction of the alternate MXI1-0 isoform followed by a long-term induction of both the MXI1-0 and MXI1 isoforms. Importantly, knock-down of MXI1 had limited effect on MYC/MYCN activity under hypoxia, an observation that might be related to the different functional attributes of the two MXI1 isoforms.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas Supressoras de Tumor
/
Fatores de Transcrição Hélice-Alça-Hélice Básicos
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Neuroblastoma
Limite:
Female
/
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Suécia