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NATH, a novel gene overexpressed in papillary thyroid carcinomas
- Source :
- Oncogene. 21:5056-5068
- Publication Year :
- 2002
- Publisher :
- Springer Science and Business Media LLC, 2002.
-
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.
- Subjects :
- Cancer Research
Time Factors
Nath
endocrine system diseases
Blotting, Western
Molecular Sequence Data
In situ hybridization
Biology
Transfection
Thyroid carcinoma
Acetyltransferases
Complementary DNA
Genetics
medicine
Animals
Humans
Amino Acid Sequence
N-Terminal Acetyltransferase E
RNA, Messenger
Thyroid Neoplasms
Northern blot
Cloning, Molecular
Molecular Biology
In Situ Hybridization
N-Terminal Acetyltransferase A
Messenger RNA
Base Sequence
Reverse Transcriptase Polymerase Chain Reaction
cDNA library
Thyroid
Molecular biology
Carcinoma, Papillary
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
COS Cells
Cell Division
Subjects
Details
- ISSN :
- 14765594 and 09509232
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Oncogene
- Accession number :
- edsair.doi.dedup.....58195d0bd9ba3372a27659558fb312a7
- Full Text :
- https://doi.org/10.1038/sj.onc.1205687