Iodide symporter gene expression in normal and transformed rat thyroid cells.
OBJECTIVE
Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells.


METHODS
Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability.


RESULTS
NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect 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 compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of 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 affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.
Trapasso
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Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgian, Università di Catanzaro, 88100 Catanzaro, Italy.
Iuliano
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R
Chiefari
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Arturi
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Stella
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Filetti
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Fusco
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Russo
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D
D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D027981:Symporters; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D000099209:Sodium-Iodide Symporters
D002352:Carrier Proteins; D005576:Colforsin; D000242:Cyclic AMP; D007328:Insulin; D007454:Iodides; D007455:Iodine; D008565:Membrane Proteins; D012333:RNA, Messenger; D027981:Symporters; D013755:Tetradecanoylphorbol Acetate; D013972:Thyrotropin; D000099209:Sodium-Iodide Symporters