CLONING OF THE HUMAN SODIUM-IODIDE SYMPORTER PROMOTER AND CHARACTERIZATION IN A DIFFERENTIATED HUMAN THYROID-CELL LINE, KAT-50

Elucidation of the regulation of human sodium-iodide symporter (hNIS) gene expression is critical to understanding its effects on iodide con centration abilities of thyroid and thyroid carcinomas. To explore thi s issue, a 1.2-kb portion of the 5'-flanking region of the hNIS gene w as isolated and characterized. Transient transfections with chimeric l uciferase-reporter constructs into a differentiated human thyroid cell line, KAT-50, as well as non-thyroidal cells, defined an active promo ter with tissue-specificity. Reverse-transcriptase polymerase chain re action analysis for hNIS mRNA expression in normal human tissues was p ositive in thyroid, salivary gland, omentum, and gallbladder. KAT-50 c ells expressed hNIS mRNA and were capable of thyrotropin-responsive io dide uptake in vitro. Despite the failure to exhibit iodide concentrat ion in clinical anaplastic carcinoma tumors, 4 of 5 cell lines from th is cancer phenotype expressed hNIS mRNA. Definition of the active prom oter provides further insights and tools to uncover new approaches to use of radioiodine for therapy of thyroid carcinomas.