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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.

Titel:	Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells.
Autor/in / Beteiligte Person:	Akagi, T ; Luong, QT ; Gui, D ; Said, J ; Selektar, J ; Yung, A ; Bunce, CM ; Braunstein, GD ; Koeffler, HP
Link:	Zum Volltext
Zeitschrift:	British journal of cancer, Jg. 99 (2008-09-02), Heft 5, S. 781
Veröffentlichung:	2002- : London : Nature Publishing Group on behalf of Cancer Research UK ; <i>Original Publication</i>: London, Lewis., 2008
Medientyp:	academicJournal
ISSN:	1532-1827 (electronic)
DOI:	10.1038/sj.bjc.6604544
Schlagwort:	Base Sequence CCAAT-Enhancer-Binding Protein-beta genetics Cell Line, Tumor DNA Methylation DNA Primers Hepatocyte Nuclear Factor 3-beta genetics Humans Immunohistochemistry Nuclear Proteins genetics Reverse Transcriptase Polymerase Chain Reaction Thyroid Neoplasms pathology Thyroid Nuclear Factor 1 Transcription Factors genetics CCAAT-Enhancer-Binding Protein-beta physiology Gene Expression Regulation, Neoplastic physiology Hepatocyte Nuclear Factor 3-beta physiology Nuclear Proteins physiology Symporters genetics Thyroid Neoplasms genetics Transcription Factors physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Br J Cancer] 2008 Sep 02; Vol. 99 (5), pp. 781-8. MeSH Terms: CCAAT-Enhancer-Binding Protein-beta / physiology ; Gene Expression Regulation, Neoplastic / physiology ; Hepatocyte Nuclear Factor 3-beta / physiology ; Nuclear Proteins / physiology ; Symporters / genetics ; Thyroid Neoplasms / genetics ; Transcription Factors / *physiology ; Base Sequence ; CCAAT-Enhancer-Binding Protein-beta / genetics ; Cell Line, Tumor ; DNA Methylation ; DNA Primers ; Hepatocyte Nuclear Factor 3-beta / genetics ; Humans ; Immunohistochemistry ; Nuclear Proteins / genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Thyroid Neoplasms / pathology ; Thyroid Nuclear Factor 1 ; Transcription Factors / genetics References: Biochem Biophys Res Commun. 1996 Mar 7;220(1):86-93. (PMID: 8602863) ; Science. 2000 Aug 25;289(5483):1357-60. (PMID: 10958784) ; J Clin Endocrinol Metab. 1997 Aug;82(8):2633-8. (PMID: 9253346) ; Biochim Biophys Acta. 1993 Jun 8;1154(1):65-82. (PMID: 8507647) ; Surgery. 1998 Dec;124(6):1100-5. (PMID: 9854590) ; Cancer Res. 2004 Jun 15;64(12):4137-47. (PMID: 15205324) ; Endocr Rev. 1994 Apr;15(2):202-32. (PMID: 8026388) ; Clin Cancer Res. 2006 Sep 15;12(18):5570-7. (PMID: 17000694) ; Exp Cell Res. 2006 Jul 1;312(11):2054-65. (PMID: 16624284) ; Nat Genet. 1998 May;19(1):87-90. (PMID: 9590297) ; J Clin Endocrinol Metab. 2003 Sep;88(9):4440-5. (PMID: 12970322) ; Trends Endocrinol Metab. 1999 May;10(4):164-167. (PMID: 10322412) ; J Clin Endocrinol Metab. 1999 Jul;84(7):2449-57. (PMID: 10404820) ; EMBO J. 2001 Dec 3;20(23):6712-23. (PMID: 11726507) ; Thyroid. 2005 Mar;15(3):197-204. (PMID: 15785238) ; Int J Cancer. 2005 Sep 1;116(3):407-14. (PMID: 15818620) ; Curr Drug Targets Immune Endocr Metabol Disord. 2004 Sep;4(3):175-80. (PMID: 15379720) ; Gene Expr. 1997;6(6):371-85. (PMID: 9495318) ; Cancer Res. 2001 May 1;61(9):3640-6. (PMID: 11325833) ; Cancer Res. 2001 Dec 15;61(24):8917-23. (PMID: 11751417) ; Genes Dev. 1996 Jan 1;10(1):60-9. (PMID: 8557195) ; Blood. 2005 Oct 15;106(8):2827-36. (PMID: 15985538) ; Biochem Biophys Res Commun. 1997 Nov 26;240(3):832-8. (PMID: 9398654) ; Biochimie. 1999 Apr;81(4):389-96. (PMID: 10401674) ; BMC Cancer. 2005 Jul 19;5:80. (PMID: 16029487) ; Cancer Res. 1996 Feb 15;56(4):765-71. (PMID: 8631011) Substance Nomenclature: 0 (CCAAT-Enhancer-Binding Protein-beta) ; 0 (DNA Primers) ; 0 (FOXA2 protein, human) ; 0 (NKX2-1 protein, human) ; 0 (Nuclear Proteins) ; 0 (Symporters) ; 0 (Thyroid Nuclear Factor 1) ; 0 (Transcription Factors) ; 135845-92-0 (Hepatocyte Nuclear Factor 3-beta) ; 4XE5NDT4K1 (sodium-iodide symporter) Entry Date(s): Date Created: 20080807 Date Completed: 20080917 Latest Revision: 20211020 Update Code: 20231215 PubMed Central ID: PMC2528161

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Induction of sodium iodide symporter gene and molecular characterisation of HNF3 beta/FoxA2, TTF-1 and C/EBP beta in thyroid carcinoma cells.