Expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor genes in neuroblastoma, medulloblastoma, and other cells lines.
We evaluated expression of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor (GluR) genes by reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blotting in nine established cell lines: rat CG-4 (oligodendroglial lineage) and RINm5F insulinoma cells; human CHP134, SMS-KCNR, SKNSH, and Nb69 neuroblastoma cells; and human D384Med, D425Med, and D458Med medulloblastoma cells. CG-4 expressed mRNAs encoding GluR2-7, KA-1, and KA-2 non-NMDA GluR (Yoshioka et al.: J Neurochem 64:2442-2448, 1995) and NR1 (NMDAR1) and NR2D NMDA GluR. After differentiation to oligodendrocyte-like cells, CG-4 also expressed NR2B mRNA. Rat insulinoma cells expressed GluR5 and KA-2 non-NMDA and NR1 and NR2D NMDA GluR mRNAs. The four human neuroblastoma lines all expressed mRNAs encoding GluR2-4, 6, 7 and KA-1 non-NMDA and NR1 NMDA GluR, and the three human medulloblastoma cell lines all expressed mRNAs encoding GluR1, 6 and KA-1, but none of the NMDA GluRs. Whereas CG-4 is susceptible to kainate excitotoxicity, treatment of insulinoma, neuroblastoma, and medulloblastoma lines with L-glutamate, kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), or NMDA failed to cause cell damage or to augment 45Ca2+ influx. Thus, despite expressing a variety of non-NMDA and NMDA GluR genes, the human neuroblastoma and medulloblastoma and rat insulinoma lines failed to assemble Ca(2+)-permeable NMDA or non-NMDA GluR channels. This failure confers protection against excitotoxicity and may contribute to progression of tumors of these types.
Yoshioka
A
A
Division of Oncology, Children's Hospital of Philadelphia, Pennsylvania, USA.
Ikegaki
N
N
Williams
M
M
Pleasure
D
D
D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D005971:Glutamates / Q000633:toxicity; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D008527:Medulloblastoma / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D005971:Glutamates; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium