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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance
Radiotherapy and Oncology, Volume 99, No. 3, Year 2011
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Description
Background: Cancer stem cells are thought to be a radioresistant population and may be the seeds for recurrence after radiotherapy. Using tumorigenic clones of retroviral immortalized human mesenchymal stem cell with small differences in their phenotype, we investigated possible genetic expression that could explain cancer stem cell radiation resistance. Methods: Tumorigenic mesenchymal cancer stem cell clones BB3 and CE8 were irradiated at varying doses and assayed for clonogenic surviving fraction. Altered gene expression before and after 2 Gy was assessed by Affymetric exon chip analysis and further validated with q-RT-PCR using TaqMan probes. Results: The CE8 clone was more radiation resistant than the BB3 clone. From a pool of 15 validated genes with altered expression in the CE8 clone, we found the enzyme nicotinamide N-methyltransferase (NNMT) more than 5-fold upregulated. In-depth pathway analysis found the genes involved in cancer, proliferation, DNA repair and cell death. Conclusions: The higher radiation resistance in clone CE8 is likely due to NNMT overexpression. The higher levels of NNMT could affect the cellular damage resistance through depletion of the accessible amounts of nicotinamide, which is a known inhibitor of cellular DNA repair mechanisms. © 2011 Elsevier Ireland Ltd. All rights reserved.
Authors & Co-Authors
D'Andrea, Filippo P.
Denmark, Aarhus
Aarhus Universitetshospital
Safwat, Akmal
Denmark, Aarhus
Aarhus Universitetshospital
Kassem, Moustapha S.
Denmark, Odense
Odense Universitetshospital
Saudi Arabia, Riyadh
College of Medicine
Gautier, Laurant
Denmark, Lyngby
Technical University of Denmark
Overgaard, Jens
Denmark, Aarhus
Aarhus Universitetshospital
Horsman, Michael R.
Denmark, Aarhus
Aarhus Universitetshospital
Statistics
Citations: 56
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1016/j.radonc.2011.05.086
e-ISSN:
18790887
Research Areas
Cancer
Genetics And Genomics
Study Design
Cross Sectional Study
Study Approach
Qualitative