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

Glutamate may cause Ca(2+) entry through Ca(2+)-permeable glutamate receptors, which in turn stimulates the anti-apoptotic signaling cascade in glioma cells. It was found that a human glioma cell line, U-87 MG, expressed subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid-type glutamate receptors (AMPAR). Ca(2+) entry through AMPAR was detected in approximately 40% of U-87 MG cells. AMPAR agonists facilitated cell proliferation in low-serum medium containing 0.5% fetal calf serum (FCS). Unexpectedly, cell proliferation by the activation of AMPAR was not detected in serum-rich medium containing 10% FCS. Overexpression of Ca(2+)-permeable AMPAR facilitated proliferation of U-87 MG cells in the low-serum condition, whereas it had again no effect in the serum-rich condition. Cell proliferation of U-87 MG cells is likely to be under the regulation of both growth factors contained in the serum and Ca(2+) entry through AMPAR, and that the latter regulation becomes evident only when serum factors are deprived of culture medium.