The transcription factor Egr1 regulates the HIF-1α gene during hypoxia
| Autor: | Ian de Belle, Sabina Sperandio, Lynda Robitaille, Jessyka Fortin, Jacques Corbeil, Roman Sasik |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Transcriptional Activation Chromatin Immunoprecipitation endocrine system Cancer Research Response element E-box Sp3 transcription factor Biomarkers Tumor Tumor Cells Cultured Humans RNA Messenger Hypoxia Promoter Regions Genetic Molecular Biology Cells Cultured Early Growth Response Protein 1 Oligonucleotide Array Sequence Analysis Sp1 transcription factor biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Prostatic Neoplasms Promoter TCF4 Hypoxia-Inducible Factor 1 alpha Subunit Activating transcription factor 2 Up-Regulation Gene Expression Regulation Neoplastic HIF1A Cancer research biology.protein |
| Zdroj: | Molecular Carcinogenesis. 48:38-44 |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.20454 |
| Popis: | Using oligonucleotide expression microarrays we have examined the modulation of gene expression in the DU145 prostate cancer cell line. Our findings confirm that the Egr1 transcription factor is rapidly and transiently upregulated by hypoxia. Furthermore, we have demonstrated that HIF-1alpha mRNA is also transiently upregulated, as is its target gene VEGF. To elucidate the mechanism of the transcriptional upregulation of the HIF-1alpha gene, we have shown that Egr1 is able to directly bind to the HIF-1alpha promoter using chromatin immunoprecipitation. We also provide evidence that the binding of Egr1 is necessary for the trans-activation of the HIF-1alpha promoter. These studies highlight the importance for the Egr1 transcription factor in the hypoxic response in cultured prostate cancer cell lines, and indicate that the response of Egr1 is upstream of HIF-1 in these cells. These studies are the first demonstration that the HIF-1alpha transcription factor is targeted directly by Egr1 in hypoxia. |
| Databáze: | OpenAIRE |
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