Abstract
In continuation to our studies on radioresistance in meningioma, here we show that radiation treatment (7Gy) induces G2/M cell cycle arrest in meningioma cells. Phosphorylation of Chk2, Cdc25c and Cdc2 were found to be key events since interference with Chk2 activation and cyclin B1/Cdc2 interaction led to permanent arrest followed by apoptosis. Irradiated cells showed recovery and formed aggressive intracranial tumors with rapid spread and morbidity. Nevertheless, knock down of uPAR with or without radiation induced permanent arrest in G2/M phase and subsequent apoptosis in vitro and in vivo. In conclusion, our data suggest that combination treatment with radiation and uPAR knock down or other inhibitors resulting in non-reversible G2/M arrest may be beneficial in the management of meningiomas.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / radiation effects
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Blotting, Western
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Brain / metabolism
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Brain / pathology
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Brain / radiation effects
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CDC2 Protein Kinase
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Carbanilides / pharmacology
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Cell Cycle Checkpoints / genetics
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Cell Cycle Checkpoints / physiology*
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Cell Cycle Checkpoints / radiation effects
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Cell Division / genetics
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Cell Division / physiology*
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Cell Division / radiation effects
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Cell Line, Tumor
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Checkpoint Kinase 2
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Cyclin B / genetics
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Cyclin B / metabolism
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Cyclin B1 / genetics
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Cyclin B1 / metabolism
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Cyclin-Dependent Kinases
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G2 Phase / genetics
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G2 Phase / physiology*
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G2 Phase / radiation effects
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Humans
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Meningioma / genetics
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Meningioma / pathology
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Meningioma / therapy
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Mice
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Mice, Nude
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Phosphorylation / drug effects
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Phosphorylation / radiation effects
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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RNA Interference
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Receptors, Urokinase Plasminogen Activator / genetics
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Receptors, Urokinase Plasminogen Activator / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Burden
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Xenograft Model Antitumor Assays / methods
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cdc25 Phosphatases / genetics
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cdc25 Phosphatases / metabolism
Substances
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Carbanilides
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Cyclin B
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Cyclin B1
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Receptors, Urokinase Plasminogen Activator
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diacetyldiphenylurea bisguanylhydrazone
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Checkpoint Kinase 2
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CHEK2 protein, human
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Chek2 protein, mouse
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Protein Serine-Threonine Kinases
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CDC2 Protein Kinase
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CDK1 protein, human
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Cyclin-Dependent Kinases
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CDC25C protein, human
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cdc25 Phosphatases