Downregulation of glutamate receptor subunit 2(3) in subependymal giant-cell tumor.

Immunohistochemical techniques were used to investigate the expression of glutamate receptor (GluR) subunits in samples of brain resected from children with and without tuberous sclerosis, using antibody to an epitope common to GluR subunits 2 and 3 [2(3)]. Our purpose was to characterize the phenotype of balloon cells in cortical tubers and tumor cells in subependymal giant-cell tumors. In cortical tubers, GluR 2(3) was expressed in the processes and cell bodies of balloon cells, demonstrating consistent immunoreactivity to vimentin. In subependymal giant-cell tumors, tumor cells also exhibited consistent immunoreactivity to vimentin but only faint immunoreactivity to GluR 2(3). The reason for the expression of subunit 2(3) in tubers but not in subependymal giant-cell tumors remains unknown. However, if one assumes that the presence of subunit 2 substantially reduces calcium conductance through alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid channel and maintains intracellular calcium homeostasis, one could speculate that downregulation of subunit 2(3) in tumor cells could result in increased calcium flux into these cells, causing tumorigenesis. Another explanation may be that receptor subunits cannot be produced sufficiently in tumor cells. Moreover, the pathogenetic pathways between balloon and giant-cells are distinctly different, despite the similarity in their phenotypical pathologic features.