TRAIL induces proliferation of human glioma cells by c-FLIPL-mediated activation of ERK1/2 |
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Authors: | U Vilimanovich V Bumbasirevic |
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Institution: | (1) Institute of Histology and Embryology, Faculty of Medicine, University of Belgrade, Visegradska 26, 11000 Belgrade, Serbia |
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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-FLIPL 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-FLIPL.
Received 2 November 2007; received after revision 14 December 2007; accepted 21 December 2007 |
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Keywords: | TRAIL apoptosis proliferation c-FLIP ERK1/2 glioma |
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