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 oligo nucleotide microarrays was done. Moreover, confirmation of altered expressi on was performed by whole cell patch clamp, immunohistochemical staining, a nd RT-PCR. Our results identified several ion and solute transport-related genes, such as N-methyl-D-aspartate (NMDA) receptors, alpha -amino-3-hydrox y-5-methyl-4-isoxazole propionate (AMPA)-2 receptors, GABA(A) receptor subu nits alpha3, beta1, beta2, and beta3, the glutamate transporter, the glutam ate/aspartate transporter II, the potassium channel K(V)2.1, hK(V)beta3, an d 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, nicoti namide N-methyltransferase, murine double minute 2 (MDM2), and epithelin (g ranulin) are upregulated in GBMs. We also demonstrate for the first time th at the cytokine and p53 binding protein, macrophage migration inhibitory fa ctor (MIF), appears upregulated in GBMs. These results indicate that the mo dulation of ion and solute transport genes and heretofore unsuspected cytok ines (i.e., MIF) may have profound implications for brain tumor cell biolog y and thus may identify potential useful therapeutic targets in GBMs.