Regulation of Sodium-iodine Symporter Expression by Retinoic Acid in Thyroid Cancer Cell Lines / 대한내분비외과학회지

ABSTRACT

PURPOSE: Response to radioiodine therapy for thyroid cancer is related to the loss of sodium-iodine symporter protein caused by dedifferentiation of thyroid cancer cells. So we aimed to study mRNA expression of CD97, dedifferentiation marker, and sodium-iodine symporter after retinoic acid treatment according to retinoids receptor status. METHODS: Thyroid cancer cell lines; ARO, FRO, NPA, TPO, and FTC133 were prepared. 5µM of all trans retinoic acid were administered to each cell lines and then expression of m RNA for retinoids receptors (RARα, RARβ, RARγ, RXRα, RXRβ, RXRγ), CD97, and Sodium-Iodine symporter by RT-PCR. RESULTS: RARs and RXRs were differently expressed in each cell line. After retinoic acid treatment, relative density of retinoic acid receptor mRNA were increased by time dependently in each cell line except TPO cell line. Expression of CD97 also was decreased in every cell lines (P<0.001). Retinoic acid increased expression of sodium-iodine symporter only in FTC133 cell line (P<0.001), and TSH or forskolin did not enhance NIS expression by retinoic acid. RARβ and RXRγ were expressed only in FTC 133cell line before treatment. Induction of sodium-iodine symporter by retinoids disappeared after RARβ specific antagonist LE135 or pan RXR antagonist PA452 administration. CONCLUSION: Retinoic acid reduced expression of CD97 in five thyroid cancer cell lines. However, retinoic acid could restore sodium-iodine symporter expression in only FTC 133 cell line specifically containing RARβ and RXRγ. Restoration of sodium-iodine symporter expression by retinoic acid is related to RARβ and RXRγ expression.