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 manifests the polarised epithelial phenotype, does not express any of the thyroid functional properties. Two transcription factors, TTF-1 and Pax-8, have been implicated in thyroid specific expression of the thyroglobulin 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 results in activation of thyroglobulin gene expression. If the expression 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 transfection of TTF-1 expression vectors in non-thyroid cell types did not result in thyroglobulin gene expression, it is suggested that Pax-8, in addition, perhaps, to a specific cellular environment, might be required for thyroid specific expression of the thyroglobulin gene.
Mascia
A
A
Centro di Endocrinologia ed Oncologia Sperimentale del CNR - Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.
De Felice
M
M
Lipardi
C
C
Gentile
R
R
Calì
G
G
Zannini
M
M
Di Lauro
R
R
Nitsch
L
L
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D007150:Immunohistochemistry; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012136:Respiratory Syncytial Viruses / Q000235:genetics; D013954:Thyroglobulin / Q000096:biosynthesis / Q000235:genetics*; D013961:Thyroid Gland / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014162:Transfection
D004268:DNA-Binding Proteins; C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; C499497:Pax8 protein, rat; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000074482:Thyroid Nuclear Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D013954:Thyroglobulin