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Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells.

Publication ,  Journal Article
Knight, MJ; Riffkin, CD; Muscat, AM; Ashley, DM; Hawkins, CJ
Published in: Oncogene
September 13, 2001

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.

Duke Scholars

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

September 13, 2001

Volume

20

Issue

41

Start / End Page

5789 / 5798

Location

England

Related Subject Headings

  • bcl-X Protein
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • TNF-Related Apoptosis-Inducing Ligand
  • Proto-Oncogene Proteins c-bcl-2
  • Oncology & Carcinogenesis
  • Membrane Glycoproteins
  • Ligands
  • Humans
  • Glioma
 

Citation

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MLA
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Knight, M. J., Riffkin, C. D., Muscat, A. M., Ashley, D. M., & Hawkins, C. J. (2001). Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene, 20(41), 5789–5798. https://doi.org/10.1038/sj.onc.1204810
Knight, M. J., C. D. Riffkin, A. M. Muscat, D. M. Ashley, and C. J. Hawkins. “Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells.Oncogene 20, no. 41 (September 13, 2001): 5789–98. https://doi.org/10.1038/sj.onc.1204810.
Knight MJ, Riffkin CD, Muscat AM, Ashley DM, Hawkins CJ. Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene. 2001 Sep 13;20(41):5789–98.
Knight, M. J., et al. “Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells.Oncogene, vol. 20, no. 41, Sept. 2001, pp. 5789–98. Pubmed, doi:10.1038/sj.onc.1204810.
Knight MJ, Riffkin CD, Muscat AM, Ashley DM, Hawkins CJ. Analysis of FasL and TRAIL induced apoptosis pathways in glioma cells. Oncogene. 2001 Sep 13;20(41):5789–5798.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

September 13, 2001

Volume

20

Issue

41

Start / End Page

5789 / 5798

Location

England

Related Subject Headings

  • bcl-X Protein
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • TNF-Related Apoptosis-Inducing Ligand
  • Proto-Oncogene Proteins c-bcl-2
  • Oncology & Carcinogenesis
  • Membrane Glycoproteins
  • Ligands
  • Humans
  • Glioma