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Physiol. Genomics 5: 21-33, 2001;
1094-8341/01 $5.00
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Received 1 August 2000; accepted in final form 14 December 2000.
Physiological Genomics 5:21-33 (2001)
1094-8341/01 $5.00 © 2001 American Physiological Society

Differential gene expression profiling in human brain tumors

JAMES M. MARKERT1, CATHERINE M. FULLER2, G. YANCEY GILLESPIE1, JAMES K. BUBIEN2, LEE ANNE MCLEAN2, ROBERT L. HONG3, KAILIN LEE3, STEVEN R. GULLANS3, TIMOTHY B. MAPSTONE4 and DALE J. BENOS2

1 Department of Surgery
2 Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005
3 Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
4 Department of Neurosurgery, Emory University, Atlanta, Georgia 30322

Gene expression profiling of three human temporal lobe brain tissue samples (normal) and four primary glioblastoma multiforme (GBM) tumors using oligonucleotide microarrays was done. Moreover, confirmation of altered expression was performed by whole cell patch clamp, immunohistochemical staining, and RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-D-aspartate (NMDA) receptors, {alpha}-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABAA receptor subunits {alpha}3, {beta}1, {beta}2, and {beta}3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel KV2.1, hKV{beta}3, and the sodium/proton exchanger 1 (NHE-1), that are all downregulated in the tumors compared with the normal tissues. In contrast, aquaporin-1, possibly aquaporins-3 and -5, and GLUT-3 message appeared upregulated in the tumors. Our results also confirmed previous work showing that osteopontin, nicotinamide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (granulin) are upregulated in GBMs. We also demonstrate for the first time that the cytokine and p53 binding protein, macrophage migration inhibitory factor (MIF), appears upregulated in GBMs. These results indicate that the modulation of ion and solute transport genes and heretofore unsuspected cytokines (i.e., MIF) may have profound implications for brain tumor cell biology and thus may identify potential useful therapeutic targets in GBMs.

glioblastoma; glutamate transporters; amiloride; NMDA receptors; BNaC; potassium channels; gene microarrays; patch clamp; reverse transcription-polymerase chain reaction; immunohistochemistry




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