Thyroid Transcription Factor-1 Activity Is Required For the Proliferation of Human Thyroid Cancer Cells 8505C - Thyroid Transcription Factor-1 Activity Is Required For the Proliferation of Human Thyroid Cancer Cells 8505C - Open Access Pub

Thyroid transcription factor-1 (TTF-1) is known to play key roles in thyroid organogenesis, in thyroid cell proliferation and in the expression of genes involved in thyroid differentiated function. Many human thyroid cancer cell lines keep producing TTF-1 despite the loss of differentiated gene expression, raising a question about the role of the factor in these cells. In order to investigate this point, we used a chimeric protein acting as a functional antagonist of TTF-1 transcriptional activity that was expressed conditionally in 8505C cells originating from an anaplastic thyroid carcinoma. We observed a growth arrest of 8505C thyroid cancer cells when the endogenous TTF-1 transcriptional activity was inhibited. It correlated with decreased levels of several mRNAs encoding positive effectors of cell proliferation like CDK1 and cyclinB1, and increased levels of various mRNAs encoding negative regulators of cell division like CDKN2B and DUSP6. In conclusion, the persistence of TTF-1 expression observed in the dedifferentiated human thyroid cancer cell line 8505C reflects the need of TTF-1 activity for the proliferation of these tumor cells. DOI10.14302/issn.2574-4496.jtc-15-838 Thyroid transcription factor-1 (TTF-1), also known as Nkx2.1 or T/ebp, is a homeodomain protein encoded by the Titf1 gene that is present in the thyroid, in lung epithelium, in the posterior pituitary and in a few restricted areas in the brain of the adult organism 1. In the thyroid, TTF-1 plays critical roles in organogenesis 1, 2, in thyroid cell proliferation 3 and in the transcriptional control of genes involved in thyroid hormones synthesis 4. Mice lacking a functional Titf1 gene fail to develop the thyroid gland 5. Also, inactivating mutations in the human Titf1 gene have been associated with developmental and/or functional thyroid defects 6. Thyroid cancer is the most frequent endocrine cancer 7. Whereas it remains often in a relatively benign form, it leads to a high death rate in its most aggressive form. Various cell lines have been derived from human thyroid tumors. Most of them present a dedifferentiated phenotype evidenced by the loss of expression of thyroid-specific genes like, thyroglobulin, thyroperoxidase and thyrotropin receptor genes 8. However, nearly all of these cells still express the Titf1 gene. Very recent data indicate that this is also the case in thyroid tumors in vivo 9. The persistence of Titf1 gene expression in dedifferentiated thyroid tumor cells raises the question as to whether the presence of this transcription factor would still be required