Molekulare Charakterisierung von Glutamat-Rezeptoren in humanen Tumoren

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Glutamate N-methyl-D-aspartate (NMDA) and ¿-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonists, which have been developed primarily for neurological indications, elicit potent anticancer effects in a variety of human cancers in vitro and in vivo. In the context of this project we plan to investigate the expression and intracellular localization of NMDA and AMPA receptor subunits, which have been extensively characterized in neuronal tissue, in various human cancers by means of RT-PCR analysis, immunocytochemistry and confocal microscopy. We will examine functional significance of the different subunits for cancer cell proliferation, migration and survival by blocking their expression by means of RNA interference using lentiviral vectors. Furthermore, we want to identify protein partners which interact with glutamate receptor subunits in cancer cells using immunoprecipitation combined with SDS-PAGE. Isolated interaction protein partner candidates will be subsequently subjected to sequence analysis using matrix-assisted laser desorption/ionization mass spectroscopy (MALDI-MS).