Document Detail

Transfection of a human glioblastoma cell line with liver-type glutaminase (LGA) down-regulates the expression of DNA repair gene MGMT and sensitizes the cells to alkylating agents.
MedLine Citation:
PMID:  22888977     Owner:  NLM     Status:  Publisher    
O(6) -methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein promoting resistance of tumor cells to alkylating chemotherapeutic agents. Glioma cells are particularly resistant to this class of drugs which include temozolomide (TMZ) and carmustine (BCNU). A previous study using the RNA microarray technique showed that decrease of MGMT mRNA stands out among the alterations in gene expression caused by the cell growth-depressing transfection of a T98G glioma cell line with liver-type glutaminase (LGA) (Szeliga M. et al., Glia, 2009). Here we show that stably LGA-transfected cells (TLGA) exhibit decreased MGMT protein expression and activity as compared to non-transfected or mock transfected cells (controls). However, the decrease of expression occurs in the absence of changes in the methylation of the promoter region, indicating that LGA circumvents, by an as yet unknown route, the most common mechanism of MGMT silencing. TLGA turned out to be significantly more sensitive to treatment with 100-1000 μM of TMZ and BCNU in the acute cell growth inhibition assay (MTT). In the clonogenic survival assay, TLGA cells displayed increased sensitivity even to 10 μM TMZ and BCNU. Our results indicates that enrichment with LGA, in addition to inhibiting glioma growth, may facilitate chemotherapeutic intervention. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Monika Szeliga; Agata Zgrzywa; Marta Obara-Michlewska; Jan Albrecht
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-13
Journal Detail:
Title:  Journal of neurochemistry     Volume:  -     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Department of Neurotoxicology, Mossakowski Medical Research Centre, Pol Acad Sci, Warsaw, Poland.
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