Disrupted co-ordination of Pax-8 and thyroid transcription factor-1 gene expression in a dedifferentiated rat thyroid tumour cell line derived from FRTL-5

C J van der Kallen, D C Spierings, J H Thijssen, M A Blankenstein, T W de Bruin

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21 Citations (Scopus)

Abstract

The mutant rat thyroid cell line FRTL-5/TA, isolated from a non-functional tumour which originated spontaneously from wild-type FRTL-5 cells, shows autonomous TSH-independent growth and loss of the thyroid-specific phenotype, lacking thyroid-specific expression of thyroglobulin (Tg) and thyroid peroxidase (TPO) genes. To investigate the role of the transcription factors Pax-8 and thyroid transcription factor-1 (TTF-1) in rat thyroid tumorigenesis, RNA expression of these two thyroid-specific nuclear factors was measured in FRTL-5/TA tumour cells and compared with the expression in wild-type FRTL-5 cells. TTF-1 gene expression was similar to that in wild-type FRTL-5, and showed a similar down-regulation after stimulation with TSH. The finding suggested normal TTF-1 mRNA and protein expression in both cell lines. By contrast, Pax-8 mRNA transcript signal was markedly reduced in FRTL-5/TA cells, reaching levels as low as 8% of the normal, basal level in FRTL-5 cells. These data indicated that the loss of thyroid-specific expression of Tg and TPO genes in FRTL-5/TA cells was not related to changes in TTF-1 gene expression but rather to reduced Pax-8 gene expression. It was concluded that a disruption of the co-ordinated expression of TTF-1 and Pax-8 is implicated in the loss of thyroid phenotype of FRTL-5/TA cells in terms of reduced Tg and TPO expression.

Original languageEnglish
Pages (from-to)377-382
Number of pages6
JournalJournal of endocrinology
Volume150
Issue number3
DOIs
Publication statusPublished - Sep-1996

Keywords

  • Animals
  • Blotting, Northern
  • Cell Line
  • DNA-Binding Proteins/genetics
  • Gene Expression/drug effects
  • Homeodomain Proteins/genetics
  • Iodide Peroxidase/genetics
  • Nuclear Proteins/genetics
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • RNA, Messenger/analysis
  • Rats
  • Thyroglobulin/genetics
  • Thyroid Gland/metabolism
  • Thyroid Neoplasms/metabolism
  • Thyroid Nuclear Factor 1
  • Thyrotropin/pharmacology
  • Trans-Activators/genetics
  • Transcription Factors/genetics
  • Tumor Cells, Cultured

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