Serum-dependence of AMPA receptor-mediated proliferation in glioma cells

Abstract

Glutamate may cause Ca²⁺ entry through Ca²⁺-permeable glutamate receptors, which in turn stimulates the anti-apoptotic signaling cascade in glioma cells. Here, we found that a human glioma cell line, U-87 MG, expressed GluR1, GluR2 and GluR3 subunits of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid-type glutamate receptors (AMPARs). Approximately 20% of GluR2 was expressed in the unedited form, which is known to assemble Ca²⁺-permeable AMPARs. Ca²⁺ entry through the activation of these receptors by AMPA was detected clearly in approximately 20% of U-87 MG glioma cells. Cell proliferation assays revealed that the application of AMPA or glutamate facilitated cell proliferation by activating AMPARs in low-serum medium containing 0.5% fetal calf serum (FCS). Unexpectedly, cell proliferation by the activation of AMPARs was not detected in serum-rich medium containing 10% FCS. Overexpression of the unedited form of GluR2 (GluR2Q) by adenoviral-mediated gene transfer markedly increased the Ca²⁺ entry into U-87 MG cells. This treatment in the presence of glutamate facilitated proliferation and migration of U-87 MG cells in the low-serum condition, whereas it had again no effect in the serum-rich condition. It is therefore likely that cell proliferation and migration of U-87 MG cells are under the regulation of growth factors contained in the serum as well as Ca²⁺ entry through AMPARs, and that the latter regulation becomes evident only when serum factors are deprived of culture medium. [J Physiol Sci. 2006;56 Suppl:S117]