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  • Original Paper
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NATH, a novel gene overexpressed in papillary thyroid carcinomas

Oncogene volume 21, pages 5056–5068 (2002)Cite this article

Abstract

In this study a replica cDNA screening (RCS) approach to identify genes differentially expressed in papillary thyroid carcinomas (PTC) was used, as compared to non-neoplastic thyroid tissues. RCS is based on hybridization of radioactively labeled cDNA probes made from the biopsies to replica membranes with 15 000 clones from a PTC cDNA library. Among the genes overexpressed in PTC, and especially in clinically aggressive tumors with histologic evidence of poorly differentiated or undifferentiated areas, a novel gene named NATH was found. NATH has two mRNA species, 4.6 and 5.8 kb, both harboring the same open reading frame encoding a putative protein of 866 amino acids. The NATH protein is homologous to yeast N-acetyltransferase (NAT)1 and to mouse NARG1 (mNAT1) and contains four tetratricopeptide repeat (TPR) domains, suggesting that NATH may be part of a multiprotein complex. Overlapping RT–PCR fragments from several PTC biopsies confirmed the NATH mRNA sequence. Northern blots, semiquantitative RT–PCR experiments, TaqMan real-time RT–PCR experiments, and in situ hybridization verified the overexpression of NATH mRNA localized to tumor cells in PTC biopsies. NATH was expressed at a low level in most human adult tissues, including the normal thyroid gland. Increased NATH expression was seen especially in a Burkitt lymphoma cell line and in adult human testis. Recombinant in vitro expression showed that NATH protein was located mainly in the cytoplasm, and was present as a single protein band of the expected 105 kDa molecular weight. Heterologous expression of NATH in the papillary carcinoma cell line (NPA) and 293 cells did not alter the cellular proliferation rate. The biological function of NATH remains to be elucidated, but the overexpression in classic PTC and especially in poorly differentiated or undifferentiated components may indicate a function in the progression of papillary thyroid carcinomas.

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Acknowledgements

The authors thank Ms Anne Marstad and Ms Benedicte Rasmussen for technical assistance. Drs Oddbjørn Straume and Hans Geir Eiken are thanked for fruitful discussions and advice. This work was supported by grants from The Norwegian Cancer Society (Ø Fluge, JE Varhaug), The Norwegian Research Council (JR Lillehaug), and the Cancer Locus, Faculty of Medicine, University of Bergen (JR Lillehaug, JE Varhaug).

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Authors and Affiliations

  1. Department of Molecular Biology, University of Bergen, Bergen, N-5020, Norway

    Øystein Fluge & Johan R Lillehaug

  2. Department of Medical Genetics and Molecular Medicine, Haukeland Hospital, University of Bergen, Bergen, N-5021, Norway

    Ove Bruland

  3. Department of Pathology, The Gade Institute, Haukeland Hospital, University of Bergen, Bergen, N-5021, Norway

    Lars A Akslen

  4. Department of Surgery, Haukeland Hospital, University of Bergen, Bergen, N-5021, Norway

    Øystein Fluge & Jan E Varhaug

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  1. Øystein Fluge
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Correspondence to Øystein Fluge.

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GenBank accession for NATH mRNA: AJ314788.

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Fluge, Ø., Bruland, O., Akslen, L. et al. NATH, a novel gene overexpressed in papillary thyroid carcinomas. Oncogene 21, 5056–5068 (2002). https://doi.org/10.1038/sj.onc.1205687

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