Abstract |
TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in TRAIL-sensitive human malignant glioma cells. We show for the first time that TRAIL stimulates cell growth in TRAIL-resistant glioma cells. TRAIL-induced cell growth in resistant cells occurred through increased cell cycle progression as determined by flow cytometry and Western blot analysis of retinoblastoma protein phosphorylation. Western blot analysis of TRAIL-treated resistant cells revealed phosphorylation of ERK1/2 proteins and in vitro kinase analysis confirmed the activation of the ERK1/2 kinases. Inhibition of MEK1 eliminated both TRAIL-induced ERK1/2 activation and cell proliferation. In addition, siRNA inhibition of c-FLIP expression eliminates TRAIL-induced ERK1/2 activation and proliferation. Furthermore, overexpression of c- FLIP(L) potentiates TRAIL-induced ERK1/2 activation and proliferation of resistant glioma cells. Our results have shown for the first time that TRAIL-induced ERK1/2 activation and proliferation of TRAIL-resistant human glioma cells is dependent upon the expression of the long form of the caspase-8 inhibitor c- FLIP(L).
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Authors | U Vilimanovich, V Bumbasirevic |
Journal | Cellular and molecular life sciences : CMLS
(Cell Mol Life Sci)
Vol. 65
Issue 5
Pg. 814-26
(Mar 2008)
ISSN: 1420-682X [Print] Switzerland |
PMID | 18239851
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CASP8 and FADD-Like Apoptosis Regulating Protein
- CFLAR protein, human
- RNA, Small Interfering
- Retinoblastoma Protein
- TNF-Related Apoptosis-Inducing Ligand
- Tumor Necrosis Factor-alpha
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
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Topics |
- Apoptosis
(physiology)
- Blotting, Western
- Brain Neoplasms
(metabolism, pathology)
- CASP8 and FADD-Like Apoptosis Regulating Protein
(antagonists & inhibitors, genetics, metabolism)
- Cell Cycle
(physiology)
- Cell Proliferation
(drug effects)
- Drug Resistance, Neoplasm
- Enzyme Activation
- Flow Cytometry
- Glioma
(metabolism, pathology)
- Humans
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Phosphorylation
- RNA, Small Interfering
(pharmacology)
- Retinoblastoma Protein
(metabolism)
- TNF-Related Apoptosis-Inducing Ligand
(pharmacology)
- Tumor Cells, Cultured
- Tumor Necrosis Factor-alpha
(pharmacology)
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