Fas (APO-1/CD95) signaling pathway is intact in radioresistant human glioma cells.
Radiation-induced apoptosis can be mediated through pathways initiated by either DNA damage or ceramide-induced Fas signaling. Glioblastoma multiforme is a primary brain tumor that is highly resistant to irradiation, and U-87 MG, SF126, and T98G are glioblastoma-derived cell lines that mimic this characteristic. We found that these radioresistant glioma cells are susceptible to Fas-mediated cell death induced by treatment with either anti-Fas antibody or exogenous ceramide. Fas-mediated cell death in these cell lines is p53-independent. These data demonstrate that apoptosis can be induced by ceramide and mediated through the Fas pathway in glioma cells, although high-dose ionizing radiation fails to trigger this pathway.
Yount
G L
GL
Preuss Laboratory for Molecular Neuro-oncology, Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, 94143, USA.
Levine
K S
KS
Kuriyama
H
H
Haas-Kogan
D A
DA
Israel
M A
MA
D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002518:Ceramides / Q000494:pharmacology; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D002518:Ceramides; D019014:fas Receptor