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Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells

journal contribution
posted on 2001-09-13, 00:00 authored by M J Knight, C D Riffkin, Andrea Muscat, David Ashley, C J Hawkins
FasL and TNF-related apoptosis-inducing ligand (TRAIL) belong to a subgroup of the TNF superfamily which induce apoptosis by binding to their death domain containing receptors. In the present study we have utilized a panel of seven cell lines derived from human malignant gliomas to characterize molecular pathways through which FasL and TRAIL induce apoptosis in sensitive glioma cells and the mechanisms of resistance in cell lines which survive the death stimuli. Our findings indicate that FADD and Caspase-8 are essential for FasL and TRAIL mediated apoptosis in glioma cells. One sensitive cell line (D270) can be protected from FasL and TRAIL induced death by anti-apoptotic Bcl-2 family members while another (D645) cannot, implying that these lines may represent glioma examples of type II and type I cells respectively. For the first time we demonstrate resistance to FasL but not to TRAIL within the one glioma cell line. Furthermore, we report distinct mechanisms of resistance within different glioma lines, including downregulation of Caspase-8 in U373MG. Cycloheximide sensitized four of the resistant cell lines suggesting the presence of labile inhibitors. None of the known apoptosis inhibitors examined accounted for the observed resistance, suggesting novel inhibitors may exist in glioma cells.

History

Journal

Oncogene

Volume

20

Issue

41

Pagination

5789 - 5798

Publisher

Nature Publishing Group

Location

London, Eng.

ISSN

0950-9232

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2001, Nature Publishing Group