Iodination of proteins in TPO transfected thyroid cancer cells is independent of NIS.
This study shows that organification of radioiodide into proteins of thyroid cancer cells exogenously co-expressing the thyroid peroxidase (TPO) and the sodium/iodide symporter (NIS) is independent of NIS function. When administering (125) I to cells constitutively expressing either NIS, or TPO or NIS/TPO, next to iodide accumulation due to NIS activity, organification was exclusively observed in TPO expressing/co-expressing cells. The use of specific inhibitors for TPO and NIS showed that organification is strictly dependent of TPO and not of NIS. An identical pattern of iodoproteins migrating between approximately 75 and 200 kDa in all cell lines tested was observed. Among the five major iodoproteins, two polypeptides appear to be related and three are most probably unrelated, according to their peptide pattern. Our results significantly indicate that co-expression of TPO in NIS transfected cells mediates iodination on the one hand but on the other hand does not contribute to augmentation of a putative NIS-based radioiodide concentrator gene therapy.
Wenzel
Achim
A
Department of Internal Medicine I, University of Ulm, Robert-Koch-Strasse 8, D-89081 Ulm, Germany.
Upadhyay
Geeta
G
Schmitt
Thomas L
TL
Loos
Ulrich
U
D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001345:Autoradiography; D045744:Cell Line, Tumor; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007467:Iodoproteins / Q000032:analysis / Q000096:biosynthesis*; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000473:pathology; D014162:Transfection; D000099209:Sodium-Iodide Symporters
D001324:Autoantigens; D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase; D007455:Iodine; D007457:Iodine Radioisotopes; D007467:Iodoproteins; D033862:Iron-Binding Proteins; D011506:Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C056658:TPO protein, human