Time- and oxygen-dependent expression and regulation of NDRG1 in human brain cancer cells

被引:23
|
作者
Said, Harun Muayad [1 ]
Safari, Roghaiyeh [2 ]
Al-Kafaji, Ghada [3 ]
Ernestus, Ralf-Ingo [4 ]
Loehr, Mario [4 ]
Katzer, Astrid [5 ]
Flentje, Michael [5 ]
Hagemann, Carsten [4 ]
机构
[1] Dokuz Eylul Univ, Grad Sch Hlth Sci, Dept Mol Med, TR-35340 Izmir, Turkey
[2] Dokuz Eylul Univ, Izmir Biomed & Genome IBG Ctr, Izmir, Turkey
[3] Arabian Gulf Univ, Dept Mol Med, Coll Med & Med Sci, Manama, Bahrain
[4] Univ Wurzburg, Dept Neurosurg, Wurzburg, Germany
[5] Univ Wurzburg, Dept Radiat Oncol, Wurzburg, Germany
关键词
tumor markers; gene expression; hypoxia; transcription factors; glioblastoma multiforme; METASTASIS SUPPRESSOR GENE; HYPOXIA-INDUCIBLE TRANSCRIPTION; HEPATIC STELLATE CELLS; BREAST-CANCER; IN-VITRO; PROSTATE-CANCER; DOWN-REGULATION; C/EBP-ALPHA; HEPATOCELLULAR-CARCINOMA; PANCREATIC-CANCER;
D O I
10.3892/or.2017.5620
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
N-myc downstream-regulated 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-1 alpha-dependent and -independent pathways under hypoxic conditions. However, there are profound differences in the way NDRG1 expression is regulated by HIF-1 alpha and other transcription factors. Therefore, we aimed to define the time-dependent pattern of NDRG1 mRNA and protein expression in human glioblastoma cell lines in extreme hypoxia and after re-oxygenation as well as under normoxic conditions. Furthermore, we ascribe the regulation of NDRG1 to the transcription factors HIF-1 alpha, SP1, CEBP alpha, YB-1 and Smad7 in a time-dependent manner. The human malignant glioma cell lines U87-MG, U373 and GaMG were cultured for 1, 6 and 24 h under hypoxic (0.1% O-2) conditions and then they were re-oxygenated. The mRNA expression of NDRG1, HIF-1 alpha SP1, CEBP alpha, YB-1 and Smad7 was measured using semi-quantitative RT-PCR analysis. Their protein expression was analyzed using western blotting. Our experiments revealed that long-term (24 h), but not short-term hypoxia led to the induction of NDRG1 expression in human glioma cell lines. NDRG1 expression was found to correlate with the protein expression of HIF-1 alpha, SP1, CEBP alpha, YB-1 and Smad7. The present study suggests for the first time that SP1 regulates NDRG1 expression in glioma cells under hypoxia in a time-dependent manner along with HIF-1 alpha, CEBP alpha, YB-1 and Smad7. These molecules, each separately or in combination, may possess the potential to become target molecules for antitumor therapeutic approaches particularly in human brain tumors.
引用
收藏
页码:3625 / 3634
页数:10
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