TRANSFECTION OF TTF-1 GENE INDUCES THYROGLOBULIN GENE-EXPRESSION IN UNDIFFERENTIATED FRT CELLS

The thyroglobulin gene, the substrate for thyroid hormone biosynthesis , is not expressed in the FRT cell line, which, even though it manifes ts the polarised epithelial phenotype, does not express any of the thy roid functional properties. Two transcription factors, TTF-1 and Pax-8 , have been implicated in thyroid specific expression of the thyroglob ulin gene. FRT cells contain Pax-8 but they lack TTF-1. In this paper, we show that transfection of TTF-1 expression vectors in FRT cells re sults in activation of thyroglobulin gene expression. If the expressio n vector encoded for TTF-1-ER, a fusion gene coding for the entire TTF -1 protein fused to the hormone-binding domain of the steroid receptor , under the control of the RSV promoter, thyroglobulin gene expression was controlled by estrogen. These data provide a direct demonstration that TTF-1 activates the chromosomal thyroglobulin promoter. Since tr ansfection of TTF-1 expression vectors in non-thyroid cell types did n ot result in thyroglobulin gene expression, it is suggested that Pax-8 , in addition, perhaps, to a specific cellular environment, might be r equired for thyroid specific expression of the thyroglobulin gene. (C) 1997 Elsevier Science B.V.