The role of caspases 9 and 9-short (9S) in death ligand- and drug-induced apoptosis in human astrocytoma cells.
Caspases are essential components of the mammalian cell death machinery. Caspase 9 is positioned at the apex of the pro-apoptotic signaling cascade induced by cytochrome c release from mitochondria. The splicing variant caspase 9-short (caspase 9S) lacks the catalytic domain and may therefore act as an endogenous inhibitor of caspase 9. Here, we report that human astrocytoma and neuroblastoma cell lines strongly express caspase 9 and 9S mRNA, whereas non-neoplastic human astrocytes show little caspase 9 and 9S mRNA expression. Transient overexpression of caspase 9S protects LN-229 astrocytoma cells from CD95 ligand (CD95L)-mediated apoptosis. However, stable overexpression of either caspase 9 or caspase 9S does not alter the sensitivity of LN-18 and LN-229 astrocytoma lines to CD95L or cytotoxic drugs. We conclude that the expression levels of caspase 9 or caspase 9S do not play a major role in determining vulnerability to apoptosis in human astrocytoma cells.
Waltereit
Robert
R
Laboratory for Molecular Neuro-Oncology, Department of Neurology, University of Tuebingen, Hoppe-Seyler-Str. 3, Germany.
Weller
Michael
M
D017398:Alternative Splicing; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001254:Astrocytoma / Q000378:metabolism*; D053453:Caspase 9; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D053222:Fas Ligand Protein; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D013713:Teniposide / Q000494:pharmacology; D019076:Transgenes; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007527:Isoenzymes; D008024:Ligands; D008562:Membrane Glycoproteins; D013713:Teniposide; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases