Heterogeneity of Human Glioblastoma: Glutathione-S-Transferase and Methylguanine-Methyltransferase

The DNA repair and detoxifying enzymes, O6-methylguanine-DNA-methyltransferase (MGMT) and glutathione-S-transferase (GST), may be responsible of poor response to alkylating agents in glioblastoma treatment. The methylation of MGMT promoter and the expression of MGMT and GST were highly heterogeneous...

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Bibliographic Details
Published in:Cancer investigation 2008-01, Vol.26 (6), p.597-609
Main Authors: Juillerat-Jeanneret, Lucienne, Bernasconi, Catherine Chapuis, Bricod, Charlotte, Gros, Solange, Trepey, Sylviane, Benhattar, Jean, Janzer, Robert C.
Format: Article
Language:English
Subjects:
Alkylating agents
Alkylating Agents - pharmacology
Brain Neoplasms - drug therapy
Brain Neoplasms - enzymology
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Carmustine - pharmacology
Cell Line, Tumor
Cell Proliferation - drug effects
DNA Methylation
DNA Modification Methylases - genetics
DNA Modification Methylases - metabolism
DNA Repair Enzymes - genetics
DNA Repair Enzymes - metabolism
DNA Replication - drug effects
Dose-Response Relationship, Drug
Enzyme Inhibitors - pharmacology
Ethacrynic Acid - pharmacology
Gene Expression Regulation, Enzymologic
Gene Expression Regulation, Neoplastic
Glioblastoma
Glioblastoma - drug therapy
Glioblastoma - enzymology
Glioblastoma - genetics
Glioblastoma - pathology
Glutathione S-Transferase pi - metabolism
Glutathione Transferase - antagonists & inhibitors
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Glutathione-S-transferase (GST)
Guanine - analogs & derivatives
Guanine - pharmacology
Heterogeneity
Human
Humans
Melphalan - pharmacology
Methylguanine methyltransferase (MGMT)
Promoter Regions, Genetic
Tumor Suppressor Proteins - genetics
Tumor Suppressor Proteins - metabolism
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Summary:The DNA repair and detoxifying enzymes, O6-methylguanine-DNA-methyltransferase (MGMT) and glutathione-S-transferase (GST), may be responsible of poor response to alkylating agents in glioblastoma treatment. The methylation of MGMT promoter and the expression of MGMT and GST were highly heterogeneous in surgical specimens of human glioblastoma and in established human glioblastoma cells under 2-D and 3-D culture conditions, suggesting an intrinsic property of these cells. MGMT and GST expression did not predict the sensitivity of glioblastoma cells to alkylating agents. Combination of alkylating agents with inhibitors of GST disclosed additive effects, suggesting that inhibition of GST should be considered in glioblastoma therapy.
ISSN:0735-7907
1532-4192
DOI:10.1080/07357900802072913