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01-07-2007 | Original Article

Identification of hypoxia-induced genes in a malignant glioma cell line (U-251) by cDNA microarray analysis

Authors: Brian T. Ragel, William T. Couldwell, David L. Gillespie, Randy L. Jensen

Published in: Neurosurgical Review | Issue 3/2007

Abstract

Overcoming the metabolic restrictions of hypoxia may allow the progression of lower-grade tumors to glioblastoma multiforme. Our findings of up-regulation of HIF-1α and its downstream targets VEGF, GLUT-1, and CAIX in higher-grade gliomas support this hypothesis. We compared the gene expression profiles of the U-251 malignant glioma cell line under normoxic and hypoxic conditions to discover future research targets. U-251 cells were grown to 75% confluence and exposed to either normoxic or hypoxic conditions for 24 h. RNA was extracted, amplified, and hybridized to a cDNA microarray chip containing ~8,800 universal cellular genes. A threefold increase in mRNA expression was used as a threshold value for differential expression. Identified genes were divided into cell cycle control, stress response, and “newly connected” genes. Hybridization identified 11 hypoxia-induced genes: 1 involved with cell cycle control (CCNG2), 6 in stress response (IGFBP3, SLC2A3, GSTT2, FOS, DDIT3, AKR1C3), and 2 newly connected genes (Depp, AKAP4). One stress-related gene (AKR1C3) encodes for an enzyme that synthesizes progesterone. Of newly connected genes, the gene decidual protein induced by progesterone (Depp) showed the highest expression (4.2-fold increase). Possible future targeting for “hypoxic” glioma cells includes the targets for the AP-1 transcription factor complex (FOS), as well as blockade of the enzyme AKR1C3 with nonsteroidal anti-inflammatory drugs. Possible functions of the highly expressed gene Depp include tumor vascularization. Future studies will focus on the hypothesis that Depp is up-regulated in an autocrine fashion by the AKR1C3 enzyme in U-251 glioma cells under hypoxic conditions.

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Title: Identification of hypoxia-induced genes in a malignant glioma cell line (U-251) by cDNA microarray analysis
Authors: Brian T. Ragel
William T. Couldwell
David L. Gillespie
Randy L. Jensen
Publication date: 01-07-2007
Publisher: Springer-Verlag
Published in: Neurosurgical Review / Issue 3/2007
Print ISSN: 0344-5607
Electronic ISSN: 1437-2320
DOI: https://doi.org/10.1007/s10143-007-0070-z

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Identification of hypoxia-induced genes in a malignant glioma cell line (U-251) by cDNA microarray analysis

Abstract

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Abstract

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