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Enhanced Expression of Nicotinamide N-Methyltransferase in Human Papillary Thyroid Carcinoma Cells

Endocrinology and Diabetes Division (J.X., K.T., G.A.B., J.M.H.), Department of Pathology and Laboratory Medicine (F.M.), Veterans Affairs Medical Center, University of California School of Medicine, Los Angeles, California 90073; Novartis Genomics Research Foundation (J.S.C., J.R.W.), San Diego, California 92121; and Endocrine Research Unit, Carmel Medical Center (Z.K.), Haifa, Israel

Address all correspondence and requests for reprints to: Jerome M. Hershman, M.D., Endocrinology Division-111D, Veterans Affairs Greater Los Angeles Healthcare System, 11301 Wilshire Boulevard, Los Angeles, California 90073. E-mail: jhershmn{at}ucla.edu.

To gain an understanding of the molecular pathogenesis of thyroid cancer, we used DNA microarray to study the expression profiles of 10 different human thyroid carcinoma cell lines. These included papillary lines BHP 2-7, BHP 7-13, BHP 10-3, BHP 18-21, NPA 87, and TPC1; anaplastic lines ARO 81-1 and DRO 90-1; follicular line WRO 82-1; and medullary line HRO 85-1. Among the genes with increased expression in the cancer cell lines, a gene coding for nicotinamide N-methyltransferase (NNMT) was identified for being highly expressed only in the papillary cell lines. NNMT catalyzes N-methylation of nicotinamide and other structurally related compounds and is highly expressed in the human liver. The results were further confirmed by semiquantitative RT-PCR and Northern blot analysis. NNMT catalytic activities were determined in all of the cells described above and in additional cell lines. Significantly higher NNMT enzyme activities were detected in eight of 10 of the papillary lines and three of six of the follicular cell lines tested. Normal thyroid tissue, thyroid primary cultures, anaplastic cancer cells, and medullary cancer cells showed no or low enzyme activity. Immunohistochemical staining for NNMT of human thyroid specimens showed strong and abundant cytoplasmic reactions in the sections of papillary carcinomas, and weak or scanty reaction in the normal thyroid tissues. These results indicate that NNMT is a potential biomarker for papillary thyroid carcinoma.

This work was supported by grants from Veterans Affairs Medical Research Funds (to J.M.H. and G.A.B.).

Abbreviations: GAPDH, Glyceraldehyde-3-phosphate dehydrogenase; NNMT, nicotinamide N-methyltransferase.

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