Differential gene expression profiling in human brain tumors.
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, GABA(A) receptor subunits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutamate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, 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.
Markert
J M
JM
Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
Fuller
C M
CM
Gillespie
G Y
GY
Bubien
J K
JK
McLean
L A
LA
Hong
R L
RL
Lee
K
K
Gullans
S R
SR
Mapstone
T B
TB
Benos
D J
DJ
D051398:Aquaporin 1; D020346:Aquaporins / Q000032:analysis; D001789:Blood Group Antigens; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis; D008564:Membrane Potentials / Q000187:drug effects; D016202:N-Methylaspartate / Q000032:analysis / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013702:Temporal Lobe / Q000166:cytology / Q000502:physiology
C496020:AQP1 protein, human; D020346:Aquaporins; D001789:Blood Group Antigens; D008263:Macrophage Migration-Inhibitory Factors; D015221:Potassium Channels; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D051398:Aquaporin 1; D016202:N-Methylaspartate