Overexpression of thyroid hormone receptor β1 is associated with thyrotropin receptor gene expression and proliferation in a human thyroid carcinoma cell line

To correlate the differentiation phenotype of two human thyroid cancer cell lines with their expression of various molecular markers, we analyzed the mRNA levels of four thyroid-specific genes, including thyrotropin receptor (TSHR), thyroglobulin (Tg), thyroid transcription factor-1 (TTF-1), and paired-box containing transcription factor-8 (PAX-8) genes. The results showed a differentiation-status-related pattern in which a well-differentiated cell Line (WRO) expressed all the four genes, in contrast to an anaplastic cell line (ARO) that expressed TTF-1 and reduced levels of TSHR, but no Tg or PAX-8 gents. Furthermore, to verify the finding of concomitant loss of beta subtype thyroid hormone receptor (TR beta) and TSHR gene expression in neoplastic thyroid tumors (Bronnegard et nl. 1994,), we examined the expression levels of TR beta 1 gene in these cell Lines. Whereas the WRO cells produced an abundant amount of TR beta 1 protein detectable by immunoprecipitation, the ARO cells produced none. This new observation prompted us to investigate whether overexpression of TR beta 1 protein in ARO cells might produce changes in the differentiation phenotypes. We found that the level of expression of the TSHR gene and the proliferative index of ARO cells were significantly upregulated in the cells stably transfected with wild-type TR beta 1. These findings suggest that TR beta 1 protein overexpression can affect the differentiation phenotypes and induce more efficient cell proliferation of the anaplastic ARO cells.