Thyroidal Iodide Transport and Thyroid Cancer

Molecular Analysis of the Sodium/Iodide Symporter: Impact on Thyroid and Extrathyroid Pathophysiology

Physiological Reviews ◽

10.1152/physrev.2000.80.3.1083 ◽

2000 ◽

Vol 80 (3) ◽

pp. 1083-1105 ◽

Cited By ~ 207

Author(s):

Antonio De la Vieja ◽

Orsolya Dohan ◽

Orlie Levy ◽

Nancy Carrasco

Keyword(s):

Thyroid Cancer ◽

Molecular Analysis ◽

Posttranslational Modifications ◽

Wide Spectrum ◽

Sodium Iodide Symporter ◽

Iodide Transport ◽

Thyroid Hormone Biosynthesis ◽

Lactating Mammary Gland ◽

Transport Defect ◽

Radioiodide Therapy

The Na+/I−symporter (NIS) is an intrinsic membrane protein that mediates the active transport of iodide into the thyroid and other tissues, such as salivary glands, gastric mucosa, and lactating mammary gland. NIS plays key roles in thyroid pathophysiology as the route by which iodide reaches the gland for thyroid hormone biosynthesis and as a means for diagnostic scintigraphic imaging and for radioiodide therapy in hyperthyroidism and thyroid cancer. The molecular characterization of NIS started with the 1996 isolation of a cDNA encoding rat NIS and has since continued at a rapid pace. Anti-NIS antibodies have been prepared and used to study NIS topology and its secondary structure. The biogenesis and posttranslational modifications of NIS have been examined, a thorough electrophysiological analysis of NIS has been conducted, the cDNA encoding human NIS (hNIS) has been isolated, the genomic organization of hNIS has been elucidated, the regulation of NIS by thyrotropin and I− has been analyzed, the regulation of NIS transcription has been studied, spontaneous NIS mutations have been identified as causes of congenital iodide transport defect resulting in hypothyroidism, the roles of NIS in thyroid cancer and thyroid autoimmune disease have been examined, and the expression and regulation of NIS in extrathyroidal tissues have been investigated. In gene therapy experiments, the rat NIS gene has been transduced into various types of human cells, which then exhibited active iodide transport and became susceptible to destruction with radioiodide. The continued molecular analysis of NIS clearly holds the potential of an even greater impact on a wide spectrum of fields, ranging from structure/function of transport proteins to the diagnosis and treatment of cancer, both in the thyroid and beyond.

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Differential effects of natural flavonoids on growth and iodide content in a human Na*/I- symporter-transfected follicular thyroid carcinoma cell line

Acta Endocrinologica ◽

10.1530/eje.0.1500557 ◽

2004 ◽

pp. 557-564 ◽

Cited By ~ 28

Author(s):

JP Schroder-van der Elst ◽

D van der Heide ◽

JA Romijn ◽

JW Smit

Keyword(s):

Thyroid Cancer ◽

Thyroid Carcinoma ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Thyroid Peroxidase ◽

Thyroid Cancer Cell ◽

Iodide Uptake ◽

Iodide Transport

OBJECTIVE: Natural flavonoids (plant pigments) have been shown to inhibit thyroid peroxidase (TPO) in vitro and the growth of thyroid cancer cell lines. We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS). DESIGN AND METHODS: Cells were treated with flavonoids (0.5-50 microM) for 0, 2, 4 and 6 days; (125)I content and (125)I efflux of the cells and DNA content were measured. RESULTS: Cell growth was inhibited significantly at day 6 by most flavonoids. Eight out of ten flavonoids decreased the (125)I content of the cells at day 4. Morin did not influence the (125)I content of the cells and, surprisingly, myricetin increased the (125)I content of the cells. Kaempferol, apigenin, luteolin and F21388 decreased NIS mRNA expression after 15, 29 and 48 h; after 96 h NIS mRNA returned to normal. CONCLUSION: As TPO is not present in this cell line, the effects of the flavonoids on the iodide uptake are not related to organification. Myricetin was the only flavonoid studied that increased the influx and decreased the efflux of iodide. The effect of myricetin (decreased growth and increased retention of iodide) can be of therapeutic value in the radioiodide treatment of thyroid carcinoma.

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