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Titel: Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance
Type: Journal articleJournal article
Person(er):
Forfatter:  D’Andrea, Filippo P.
Aarhus University Hospital, Denmark, Department of Experimental Clinical Oncology

Forfatter:  Safwat, Akmal
Aarhus University Hospital, Denmark, Department of Experimental Clinical Oncology

Forfatter:  Kassem, Moustapha
Odense University Hospital, Denmark, Laboratory for Molecular Endocrinology

Forfatter:  Gautier, Laurent (Cwisno: 15698)
Technical University of Denmark
Email:

Forfatter:  Overgaard, Jens
Aarhus University Hospital, Denmark, Department of Experimental Clinical Oncology

Forfatter:  Horsman, Michael R.
Aarhus University Hospital, Denmark, Department of Experimental Clinical Oncology
Uddrag: BackgroundCancer 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. MethodsTumorigenic 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 2Gy was assessed by Affymetric exon chip analysis and further validated with q-RT-PCR using TaqMan probes. ResultsThe 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. ConclusionsThe 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.
Publiceret: in journal: Radiotherapy & Oncology (ISSN: 0167-8140) (DOI: http://dx.doi.org/10.1016/j.radonc.2011.05.086), vol: 99, issue: 3, pages: 373-378, 2011
DOI:
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