Cancer stem cell overexpression of nicotinamide N-methyltransferase enhances cellular radiation resistance

Radiother Oncol. 2011 Jun;99(3):373-8. doi: 10.1016/j.radonc.2011.05.086. Epub 2011 Jun 29.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Cell Cycle / radiation effects
  • Chromosome Aberrations
  • Cytokines / metabolism
  • Exons
  • Gene Expression
  • Humans
  • Mesenchymal Stem Cells / enzymology*
  • Mesenchymal Stem Cells / radiation effects*
  • Neoplastic Stem Cells / enzymology*
  • Neoplastic Stem Cells / radiation effects*
  • Nicotinamide N-Methyltransferase / metabolism*
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Phenotype
  • Radiation Tolerance / genetics*
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation


  • Cytokines
  • Nicotinamide N-Methyltransferase
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human