Akademik Veri Yönetim Sistemi
FEBS OPEN BIO, cilt.12, ss.92, 2022 (SCI-Expanded)
Hypoxia-inducible factor-1 (HIF-1) is a key regulator of tumor cell hypoxia of several genes related to oxygen homeostasis in response to hypoxic stress. Carbonic anhydrase 9 (CA9) has been found to be a stable marker of acute or chronic hypoxia. N-myc downstreamregulated gene 1 (NDRG1) is a tumor suppressor with the potential to suppress metastasis, invasion, and migration of cancer cells. It is regulated under stress conditions such as starvation or hypoxia. NDRG1 regulation is both induced and controlled by HIF-1a-dependent and -independent pathways under hypoxic conditions. We aimed to define the time-dependent pattern of CA9 and NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Here, the regulation of the transcription factors HIF-1a, SP1, CEBPa, YB-1, and Smad7 was examined in a time-dependent manner. The human malignant glioma cell lines U87-MG, and GaMG were cultured for 1, 6, and 24 h under hypoxic (0.1% O2) conditions with following re-oxygenation. The mRNA expression of NDRG1, CA9, HIF-1a SP1, CEBPa, YB-1, and Smad7 was measured via semi-quantitative RT-PCR analysis. Protein expression was analyzed using western blotting. Long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines while CA9 was induced upon short- and long-time hypoxic oxygenation conditions. CA9 and NDRG1 expression was found to correlate with the protein expression of HIF-1a, SP1, CEBPa, YB-1, and Smad7. These transcriptional factors, each separately or in combination, may possess the potential to become important regulative molecules that can be targetted during antitumor targetting.
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