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Promoter characterization of the rat Na+/I- symporter gene.

The Na+/I- symporter is the molecule that mediates active iodide uptake in the thyroid gland. A 16.4 kb genomic DNA fragment of the rat Na+/I- symporter gene (rNIS) was isolated, restriction mapped and a 2 kb region immediate 5' to the ATG site was sequenced. The transcription start site for rNIS was mapped to -98 nucleotide (nt) relative to the ATG translation initiation site. A series of 5' genomic DNA fragments ranging from 233 bp to 8 kb were tested for promoter activity in both thyroid and non-thyroid cells. Our results indicate that the DNA regulatory elements within 8 kb of the 5' flanking region of rNIS are not sufficient to confer thyroid-selective transcription. However, consistent with the clinical observation that NIS expression is reduced in thyroid tumors, the rNIS promoter activity is suppressed in ret/PTC1 transformed NIH3T3 cells, compared to non-transformed NIH3T3 cells.