PTTG and PBF repress the human sodium iodide symporter

Kristien Boelaert, Vicki Smith, Anna Stratford, T Kogai, Lesley Tannahill, John Watkinson, Margaret Eggo, Jayne Franklyn, Christopher McCabe

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most thyroid tumours exhibit reduced iodide uptake, although the mechanisms accounting for this remain poorly understood. Pituitary tumour transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We now show that PTTG and its binding factor PBF repress expression of sodium iodide symporter (NIS) messenger RNA (mRNA), and inhibit iodide uptake. This process is mediated at least in part through fibroblast growth factor-2. In detailed studies of the NIS promoter in rat FRTL-5 cells, PTTG and PBF demonstrated specific inhibition of promoter activity via the human upstream enhancer element (hNUE). Within this approximately 1 kb element, a complex PAX8-upstream stimulating factor 1 (USF1) response element proved critical both to basal promoter activity and to PTTG and PBF repression of NIS. In particular, repression by PTTG was contingent upon the USF1, but not the PAX8, site. Finally, in human primary thyroid cells, PTTG and PBF similarly repressed the NIS promoter via hNUE. Taken together, our data suggest that the reported overexpression of PTTG and PBF in differentiated thyroid cancer has profound implications for activity of the NIS gene, and hence significantly impacts upon the efficacy of radioiodine treatment.
Original languageEnglish
Pages (from-to)4344-4356
Number of pages13
JournalOncogene
Volume26
Issue number30
DOIs
Publication statusPublished - 5 Feb 2007

Keywords

  • PBF
  • thyroid cancer
  • PTTG
  • NIS

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