Molecular Medicine

, Volume 13, Issue 7–8, pp 415–421 | Cite as

Nicotinamide N-Methyltransferase Upregulation Inversely Correlates with Lymph Node Metastasis in Oral Squamous Cell Carcinoma

  • Davide Sartini
  • Andrea Santarelli
  • Valentina Rossi
  • Gaia Goteri
  • Corrado Rubini
  • Domenico Ciavarella
  • Lorenzo Lo Muzio
  • Monica Emanuelli


We investigated expression levels of Nicotinamide N-Methyltransferase (NNMT), an enzyme Involved In the biotransformation of many drugs and xenobiotic compounds, in oral squamous cell carcinoma (OSCC). Measurements were performed by semiquantitative RT-PCR and quantitative real-time PCR in tumor and matched adjacent healthy tissue. Interestingly, NNMT was upregulated in most of the favorable OSCCs, while no marked NNMT expression alterations between tumor and normal mucosa were detected in most of the unfavorable OSCCs. Western blot and immunohistochemical analyses also were performed and the relationship between tumor characteristics and NNMT levels in OSCC were studied to evaluate the effectiveness of NNMT as a prognostic marker in the squamous cell carcinoma of the oral cavity. In summary, the present study suggests that NNMT may have potential as a biomarker and a therapeutic target for OSCC.



We gratefully acknowledge Dr Richard Weinshilboum, Mayo Clinic, Rochester, MN, for providing NNMT antibody.


  1. 1.
    Brinkman BM, Wong DT (2006) Disease mechanism and biomarkers of oral squamous cell carcinoma. Curr. Opin. Oncol. 18:228–33.CrossRefGoogle Scholar
  2. 2.
    Carinci F et al. (2005) Potential markers of tongue tumor progression selected by cDNA microarray. Inf. J. Immunopathol. Pharmacol. 18:513–24.CrossRefGoogle Scholar
  3. 3.
    Tomioka H, Morita K, Hasegawa S, Omura K. (2006) Gene expression analysis by cDNA microarray in oral squamous cell carcinoma. J. Oral. Pathol. Med. 35:206–11.CrossRefGoogle Scholar
  4. 4.
    Lo Muzio L et al. (2005) Survivin as prognostic factor in squamous cell carcinoma of the oral cavity. Cancer Lett. 225:27–33.CrossRefGoogle Scholar
  5. 5.
    Lo Muzio L et al. (2006) Genetic analysis of oral squamous cell carcinoma by cDNA microarrays focused apoptotic pathway. Int. J. Immunopathol. Pharmacol. 19:675–82.CrossRefGoogle Scholar
  6. 6.
    Li Y et al. (2006) Serum circulating human mRNA profiling and its utility for oral cancer detection. J. Clin. Oncol. 24:1754–60.CrossRefGoogle Scholar
  7. 7.
    Rini J, Szumlanski C, Guerciolini R, Weinshilboum RM. (1989) Human liver nicotinamide N-methyltransferase, ion-pairing radiochemical assay, biochemical properties and individual variation. Clin. Chim. Acta. 186:359–74.CrossRefGoogle Scholar
  8. 8.
    Aksoy S, Szumlanski CL, Weinshilboum RM. (1994) Human liver nicotinamide N-methyltrans-ferase. cDNA cloning, expression, and biochemical characterization. J. Biol. Chem. 269:14835–40.PubMedGoogle Scholar
  9. 9.
    Aksoy S, Brandriff BF, Ward A, Little PF, Weinshilboum, RM. (1995) Human nicotinamide N-methyltransferase gene, molecular cloning, structural characterization and chromosomal localization. Genomics. 29:555–61.CrossRefGoogle Scholar
  10. 10.
    Szakacs G et al. (2004) Predicting drug sensitivity and resistance, profiling ABC transporter genes in cancer cells. Cancer Cell. 6:129–37.CrossRefGoogle Scholar
  11. 11.
    Xu J et al. (2003) Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells. J. Clin. Endocrinol. Metab. 88:4990–6.CrossRefGoogle Scholar
  12. 12.
    Myo K et al. (2005) Cyclin D1 gene numerical aberration is a predictive marker for occult cervical lymph node metastasis in TNM Stage I and II squamous cell carcinoma of the oral cavity. Cancer. 104:2709–16.CrossRefGoogle Scholar
  13. 13.
    Williams AC, Ramsden, DB. (2005) Autotoxicity, methylation and a road to the prevention of Parkinson’s disease. J. Clin. Neurosci. 12:6–11.CrossRefGoogle Scholar
  14. 14.
    Markert JM et al. (2001) Differential gene expression profiling in human brain tumors. Physiol. Genomics. 5:21–33.CrossRefGoogle Scholar
  15. 15.
    Jang JS, Cho HY, Lee YJ, Ha WS, Kim, HW. (2004) The differential proteome profile of stomach cancer, identification of the biomarker candidates. Oncol. Res. 14:491–9.CrossRefGoogle Scholar
  16. 16.
    Lim BH, Cho BI, Kim YN, Kim JW, Park ST, Lee, CW. (2006) Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification. Exp. Mol. Med. 38:455–65.CrossRefGoogle Scholar
  17. 17.
    Xu J, Capezzone M, Xu X, Hershman JM. (2005) Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells. Mol. Endocrinol. 19:527–39.CrossRefGoogle Scholar
  18. 18.
    Roessler M et al. (2005) Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer. Clin. Cancer Res. 11:6550–7.CrossRefGoogle Scholar
  19. 19.
    Yao M et al. (2005) Gene expression analysis of renal carcinoma, adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. J. Pathol. 205:377–87.CrossRefGoogle Scholar
  20. 20.
    Sartini D, Muzzonigro G, Milanese G, Pierella F, Rossi V, Emanuelli M. (2006) Identification of nicotinamide N-methyltransferase as a novel tumor marker for renal clear cell carcinoma. J. Urol. 176:2248–54.CrossRefGoogle Scholar
  21. 21.
    Rogers CD et al. (2006) Differentiating pancreatic lesions by microarray and QPCR analysis of pancreatic juice RNAs. Cancer Biol. Ther. 5:1383–9.CrossRefGoogle Scholar
  22. 22.
    Seifert R, Hoshino J, Kroger H. (1984) Nicotinamide methylation. Tissue distribution, developmental and neoplastic changes. Biochim. Biophys. Acta. 801:259–64.CrossRefGoogle Scholar
  23. 23.
    Williams AC, Ramsden DB. (2005) Nicotinamide homeostasis, a xenobiotic pathway that is key to development and degenerative diseases. Med. Hypotheses. 65:353–62.CrossRefGoogle Scholar
  24. 24.
    Zhang J. (2003) Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked? Bioassays. 25:808–14.CrossRefGoogle Scholar

Copyright information

© Feinstein Institute for Medical Research 2007

Authors and Affiliations

  • Davide Sartini
    • 1
  • Andrea Santarelli
    • 2
  • Valentina Rossi
    • 1
  • Gaia Goteri
    • 3
  • Corrado Rubini
    • 3
  • Domenico Ciavarella
    • 4
  • Lorenzo Lo Muzio
    • 4
  • Monica Emanuelli
    • 1
  1. 1.Istituto di Biotecnologie BiochimicheUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Institute of Dentistry and Stomatological Sciences, Section of Pathological Anatomy and HistopathologyPolytechnic University of MarcheAnconaItaly
  3. 3.Department of Neurosciences, Section of Pathological Anatomy and HistopathologyPolytechnic University of MarcheAnconaItaly
  4. 4.Department of Surgical SciencesUniversity of FoggiaFoggiaItaly

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