Differential gene expression profiling in human brain tumors

Abstract

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.

Quantitative Phosphoproteomics Reveals Wee1 Kinase as a Therapeutic Target in a Model of Proneural Glioblastoma

“…Reduced glutamate receptor phosphorylation, previously observed in GBM (35, 36), along with decreased phosphorylation of Dlg 2 (PSD-93), 3, and 4 (PSD-95) (37), and other neuron-specific proteins in our tumors likely reflect the differences in cellular composition between glioma and normal brain tissue (21). By comparison, phosphorylation of proteins involved in canonical oncogenic signaling networks, including ERK1/2 MAP kinases (T183/Y185 and T203/Y205 in the activation loop), PI3K regulatory subunit P85a, PDGFRα, and RTK scaffolds GAB1 and SHC, and cell cycle regulation (CDK1) were all increased in the tumor samples.…”

Increased aquaporin 1 water channel expression inhuman brain tumours

“…In that study, AQP1 immunoreactivity was found in glioblastoma cells and microvascular endothelial cells, but not normal brain parenchyma or normal microvessel endothelium. AQP1 mRNA levels have recently been shown to be increased in human glioblastoma, compared with normal human brain (Markert et al, 2001). …”

MIF loss impairs Myc-induced lymphomagenesis

“…10,11 However, based on the recently observed correlation of MIF expression levels and tumor aggressiveness it was proposed that MIF might also serve as a link between inflammation and cancer. [12][13][14][15][16][17] Within the hematopoietic system, MIF is expressed by several cell types, including B-lymphoid, 51 T-lymphoid, 52 myeloid, 53,54 and erythroid progenitor cells (OP, unpublished). Here, we provide direct evidence for MIF's involvement in malignant processes in vivo.…”

“…[6][7][8][9] Studies using neutralizing antibodies implicated MIF in the development of pathologies of acute and chronic inflammation such as allograft rejection, wound repair, glomerulonephritis, inflammatory arthritis, and septic shock. 10,11 Moreover, based on the observed correlation of MIF expression levels and clinical aggressiveness of tumors, [12][13][14][15][16] it was suggested that MIF could serve as a connection between inflammation and cancer. 17,18 However, the process by which MIF exerts its effect on target cells is not understood.…”