Enhanced Expression of NicotinamideN-Methyltransferase in Human Papillary Thyroid Carcinoma Cells

Abstract

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.

Integrin-linked kinase is a potential therapeutic target for anaplastic thyroid cancer

“…Despite this small number, the cell lines we used are among the most well established in the literature (30,32,33). We are currently working with a larger panel of cell lines to verify our findings.…”

Nicotinamide N-methyltransferase protein expression in renal cell cancer

“…Besides the strong staining in the cytoplasma of RCC cells, moderate nucleus staining was also observed in this study. While NNMT is cytoplasmic protein, its nucleus staining has also been found in normal mucosa, normal thyroid cells, goiter, and thyroid adenomas and papillary carcinomas by IHC (Xu et al, 2003;Sartini et al, 2007). The nature of the nuclear staining of NNMT needs to be further studied.…”

“…NNMT is predominantly expressed in the liver in which drug and other xenobiotic compounds are mainly metabolized by N-methylation method, and weakly expressed in other tissues such as the kidney, lung, skeletal muscle, placenta, heart, and brain (Yan et al, 1999). Recently, abnormal expression of NNMT has been reported in tumors such as papillary thyroid cancers (Xu et al, 2003;, glioblastoma, stomach adenocarcinoma (Jang et al, 2004;Lim et al, 2006), colon cancer (Roessler et al, 2005), renal carcinoma (Yao et al, 2005;Sartini et al, 2006), oral squamous cell carcinoma (Sartini et al, 2007), lung cancer (Tomida et al, 2009), and liver cancer (Kim et al, 2009). Those results indicate that NNMT may become a potential biomarker for diagnosis of tumor and may have a potential role for predicting response to radiation therapy or chemotherapy.…”

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

“…Specimens were incubated overnight with polyclonal rabbit antibody anti-human NNMT (Richard Weinshilboum, Mayo Clinic) at a dilution of 1:500. The specificity of this antibody has been described in the literature (11).…”