Iodide symporter gene expression in normal and transformed rat thyroid cells

Objective: Decrease or loss of the Na+/I- symporter (NIS) activity profound ly affects the suitability of the use of radioiodine to detect or treat met astatic thyroid tissues. The aim of our study was to verify whether specifi c oncogene abnormalities were responsible for the alteration in NIS activit y in thyroid cells. Design and methods: Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with d ifferent degrees of malignancy which had lost the iodide uptake ability. Results: NIS gene expression was up-regulated by TSH in a dose-dependent an d time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely insulin a nd 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory e ffect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA , PC HaMSV; PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compa red with the normal PC Cl 3 cells. Conversely, an almost complete absence o f NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala) and PC PyMLV cell lines. Conclusions: Our data show that oncogene activation could play a role in af fecting the iodide uptake ability in thyroid tumoral cells; different mecha nisms are involved in the oncogene-dependent loss of MS activity in transfo rmed thyroid cells.