Artikel
Egr-1 is not regulated under hypoxic conditions in human glioblastoma
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Veröffentlicht: | 20. Mai 2009 |
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Objective: It has been shown in several publications (Ellen T et al., 2007; Zhang P et al., 2007) that the transcription factor Egr-1 is regulated via hypoxia, and the authors hypothesized that Egr-1 is responsible for hypoxia induced NDRG1 gene regulation in human tumor cells. HIF-1α is the main regulator of several hypoxia-induced genes.
Methods: Egr-1 regulation level was examined in human glioblastoma cell lines like U373, U251, GaMG and U87-MG under extreme hypoxic conditions (0.1% O2), under reoxigenation after hypoxia for 24 and 48h, and under normoxic conditions (21% O2 and 5% CO2) in vitro. Protein and mRNA levels were detected via western blots and RT-PCR. Cells incubated for 24h with 100µM DFO served as positive controls for hypoxia, and β-tubulin and β-actin served as loading controls, respectively.
Results: Egr-1 was not up-regulated by hypoxic development in different glioblastoma cell lines in vitro under extreme hypoxic conditions (0.1% O2) or reoxigenation after hypoxia, neither on protein, nor on mRNA level. Furthermore, there was no association between Egr-1 expression and the expression of the hypoxia-induced HIF-1α regulated genes in a population of human glioblastoma tumor specimens examined in vitro.
Conclusions: Egr-1 regulation on protein or mRNA level as a reaction to hypoxic development in glioblastoma is not a general phenomenon. Contrarily to the previously published data, there were no hypoxic conditions that influenced Egr-1 regulation. Therefore at least in glioblastoma, HIF-1α till still can be considered as a major regulator of NDRG1 under hypoxic conditions. Further extensive analysis of tumor cells from different origins under similar physiological conditions can give more comprehensive insight concerning the degree to which Egr-1 can play a role in regulating the expression of these genes under hypoxic conditions. In our opinion, Egr-1 regulation under hypoxia is a cell specific post-translational event.