Evidence for transcriptional and posttranscriptional alterations of the sodium/iodide symporter expression in hypofunctioning benign and malignant thyroid tumors.
The uptake of iodide by epithelial thyroid cells requires the expression of a specific transporter, the Na(+)/I(-) symporter, NIS. Benign and malignant thyroid tumors of epithelial origin show a decrease up to a loss of iodide uptake activity. Previous studies of the human NIS (hNIS) gene expression in these tumors, based on the amplification of transcripts and/or immunohistochemical detection of the protein, have yielded divergent data; hNIS expression was found either increased or decreased. To get a new and integrated view of the alterations of hNIS expression in hypofunctioning thyroid tumors, we performed investigations of hNIS transcript and hNIS protein levels on the same tumors and paired normal tissue samples. HNIS, identified as a 75- to 80-kd species, was present in all normal tissue samples from euthyroid patients, but was undetectable, even at high membrane protein input, in all benign and malignant hypofunctioning thyroid tumors. By contrast, approximately 50% of tumors contained hNIS transcripts. This dissociation between transcript and protein levels was not found for the transcript and protein encoded by the PDS gene assayed in the same tumors. The hNIS transcript-positive tumors contained small amounts of low-molecular mass hNIS-immunoreactive species identified as nonglycosylated hNIS. Tumors containing the nonmature form of hNIS exhibited a predominant intracellular immunolabeling. In conclusion, our data show that benign and malignant hypofunctioning thyroid tumors either no longer express hNIS protein or express only a very low amount of nonglycosylated hNIS and indicate that the impairment of hNIS gene expression might result from alterations at both transcriptional and posttranscriptional levels.
Trouttet-Masson
Séverine
S
UMR369 INSERM /Université Claude Bernard-Lyon 1 and Institut Fédératif de Recherche 62, Faculté de Médecine Lyon-RTH Laennec, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France. u369@laennec.univ-lyon1.fr
Selmi-Ruby
Samia
S
Bernier-Valentin
Françoise
F
Porra
Valérie
V
Berger-Dutrieux
Nicole
N
Decaussin
Myriam
M
Peix
Jean-Louis
JL
Perrin
Agnès
A
Bournaud
Claire
C
Orgiazzi
Jacques
J
Borson-Chazot
Françoise
F
Franc
Brigitte
B
Rousset
Bernard
B
D015153:Blotting, Western; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007457:Iodine Radioisotopes / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011877:Radionuclide Imaging; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D000099209:Sodium-Iodide Symporters
D007457:Iodine Radioisotopes; D027981:Symporters; D000099209:Sodium-Iodide Symporters