Overexpression of thyroid hormone receptor beta 1 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 pai red-box containing transcription factor-8 (PAX-8) genes. The results showed a differentiation-status-related pattern in which a well-differentiated ce ll Line (WRO) expressed all the four genes, in contrast to an anaplastic ce ll 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 bet a subtype thyroid hormone receptor (TR beta) and TSHR gene expression in ne oplastic thyroid tumors (Bronnegard et nl. 1994,), we examined the expressi on levels of TR beta 1 gene in these cell Lines. Whereas the WRO cells prod uced an abundant amount of TR beta 1 protein detectable by immunoprecipitat ion, the ARO cells produced none. This new observation prompted us to inves tigate whether overexpression of TR beta 1 protein in ARO cells might produ ce changes in the differentiation phenotypes. We found that the level of ex pression of the TSHR gene and the proliferative index of ARO cells were sig nificantly upregulated in the cells stably transfected with wild-type TR be ta 1. These findings suggest that TR beta 1 protein overexpression can affe ct the differentiation phenotypes and induce more efficient cell proliferat ion of the anaplastic ARO cells.