Sperandio Sabina, Fortin Jessyka, Sasik Roman, Robitaille Lynda, Corbeil Jacques, de Belle Ian
Centre de Recherche du Centre Hospitalier Université Laval, Centre de Génomique, Université Laval, Québec, Canada.
Mol Carcinog. 2009 Jan;48(1):38-44. doi: 10.1002/mc.20454.
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.
我们利用寡核苷酸表达微阵列检测了DU145前列腺癌细胞系中基因表达的调控情况。我们的研究结果证实，缺氧可迅速且短暂地上调Egr1转录因子。此外，我们还证明HIF-1α mRNA及其靶基因VEGF也会短暂上调。为阐明HIF-1α基因转录上调的机制，我们通过染色质免疫沉淀法表明Egr1能够直接结合到HIF-1α启动子上。我们还提供证据表明，Egr1的结合对于HIF-1α启动子的反式激活是必要的。这些研究突出了Egr1转录因子在培养的前列腺癌细胞系缺氧反应中的重要性，并表明在这些细胞中Egr1的反应在HIF-1的上游。这些研究首次证明在缺氧状态下Egr1直接作用于HIF-1α转录因子。
