Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding glucose transporters, glycolytic enzymes, vascular endothelial growth factor, and other proteins involved in O2 homeostasis and tumor progression. The expression and transcriptional activity of the HIF-1alpha subunit is regulated by the cellular O2 concentration. We demonstrate that insulin, insulin-like growth factor (IGF)-1, and IGF-2 induce expression of HIF-1alpha, which is required for expression of genes encoding IGF-2, IGF-binding protein (IGFBP)-2 and IGFBP-3. These data provide a novel mechanism by which HIF-1alpha overexpression may occur in tumor cells and contribute to an autocrine growth factor loop.
Feldser
D
D
Institute of Genetic Medicine, Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA.
Agani
F
F
Iyer
N V
NV
Pak
B
B
Ferreira
G
G
Semenza
G L
GL
D000818:Animals; D019898:Autocrine Communication; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D009687:Nuclear Proteins; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II