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

Br J Cancer. 2008 Sep 2;99(5):781-8. doi: 10.1038/sj.bjc.6604544.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / physiology*
  • Cell Line, Tumor
  • DNA Methylation
  • DNA Primers
  • Gene Expression Regulation, Neoplastic / physiology*
  • Hepatocyte Nuclear Factor 3-beta / genetics
  • Hepatocyte Nuclear Factor 3-beta / physiology*
  • Humans
  • Immunohistochemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Symporters / genetics*
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics
  • Transcription Factors / physiology*


  • CCAAT-Enhancer-Binding Protein-beta
  • DNA Primers
  • FOXA2 protein, human
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Symporters
  • Thyroid Nuclear Factor 1
  • Transcription Factors
  • Hepatocyte Nuclear Factor 3-beta
  • sodium-iodide symporter