Induction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells
Copyright policy )Induction of sodium iodide symporter gene and molecular characterisation of HNF3β/FoxA2, TTF-1 and C/EBPβ in thyroid carcinoma cells
Thyroid carcinoma cells often do not express thyroid-specific genes including sodium iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (TG), and thyrotropin-stimulating hormone receptor (TSHR). Treatment of thyroid carcinoma cells (four papillary and two anaplastic cell lines) with histone deacetylase inhibitors (SAHA or VPA) modestly induced the expression of the NIS gene. The promoter regions of the thyroid-specific genes contained binding sites for hepatocyte nuclear factor 3 beta (HNF3 beta)/forkhead box A2 (FoxA2), thyroid transcription factor 1 (TTF-1), and CCAAT/enhancer binding protein (C/EBP beta). Quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed decreased expression of HNF3 beta/FoxA2 and TTF-1 mRNA in papillary thyroid carcinoma cell lines, when compared with normal thyroid cells. Forced expression of these genes in papillary thyroid carcinoma cells inhibited their growth. Furthermore, the CpG island in the promoter region of HNF3 beta/FoxA2 was aberrantly methylated; and treatment with 5-aza-2-deoxycytidine (5-Az) induced its expression. Immunohistochemical staining showed that C/EBP beta was localised in the nucleus in normal thyroid cells but was detected in the cytoplasm in papillary thyroid carcinoma cells. Subcellular fractionation of papillary thyroid carcinoma cell lines also demonstrated high levels of expression of C/EBP beta in the cytoplasm, suggesting that a large proportion of C/EBP beta protein is inappropriately localised in the cytoplasm. In summary, these findings reveal novel abnormalities in thyroid carcinoma cells.
- University of Birmingham United Kingdom
- University of California, San Francisco United States
- Cedars-Sinai Medical Center United States
- University of Birmingham, School of Biosciences United Kingdom
- School of Bioscience United Kingdom
Oncology and Carcinogenesis, Thyroid Nuclear Factor 1, 610, anaplastic, Cell Line, Rare Diseases, papillary, Cell Line, Tumor, Genetics, thyroid cancer, 2.1 Biological and endogenous factors, Humans, Oncology & Carcinogenesis, Thyroid Neoplasms, Aetiology, Molecular Diagnostics, Cancer, DNA Primers, Neoplastic, Tumor, Base Sequence, Symporters, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-beta, Nuclear Proteins, DNA Methylation, Immunohistochemistry, HNF3 beta/FoxA2, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, C/EBP beta, Public Health and Health Services, Hepatocyte Nuclear Factor 3-beta, Biotechnology, Transcription Factors
Oncology and Carcinogenesis, Thyroid Nuclear Factor 1, 610, anaplastic, Cell Line, Rare Diseases, papillary, Cell Line, Tumor, Genetics, thyroid cancer, 2.1 Biological and endogenous factors, Humans, Oncology & Carcinogenesis, Thyroid Neoplasms, Aetiology, Molecular Diagnostics, Cancer, DNA Primers, Neoplastic, Tumor, Base Sequence, Symporters, Reverse Transcriptase Polymerase Chain Reaction, CCAAT-Enhancer-Binding Protein-beta, Nuclear Proteins, DNA Methylation, Immunohistochemistry, HNF3 beta/FoxA2, Gene Expression Regulation, Neoplastic, Gene Expression Regulation, C/EBP beta, Public Health and Health Services, Hepatocyte Nuclear Factor 3-beta, Biotechnology, Transcription Factors
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