DISRUPTED COORDINATION OF PAX-8 AND THYROID TRANSCRIPTION FACTOR-I GENE-EXPRESSION IN A DEDIFFERENTIATED RAT-THYROID TUMOR-CELL LINE DERIVED FROM FRTL-5

The mutant rat thyroid cell line FRTL-5/TA, isolated from a non-functi onal tumour which originated spontaneously from wild-type FRTL-5 cells , shows autonomous TSH-independent growth and loss of the thyroid-spec ific 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 oi these two thyroid-sp ecific nuclear factors was measured in FRTL-5/TA tumour cells and comp ared with the expression in wild-type FRTL-5 cells. TTF-1 gene express ion was similar to that in wild-type FRTL-5, and showed a similar down -regulation after stimulation with TSH. The finding suggested normal T TF-1 mRNA and protein expression in both cell lines. By contrast, Pax- 8 mRNA transcript signal was markedly reduced in FRTL-5/TA cells, reac hing levels as low as 8% of the normal, basal level in FRTL-5 cells. T hese 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 co ncluded 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 cell s in terms of reduced Tg and TPO expression.