Regulation of the sodium/iodide symporter by retinoids--a review

• Published in: Experimental and clinical endocrinology & diabetes Vol. 109; no. 1; p. 41
• Main Author: Schmutzler, C
• Format: Journal Article
• Language: English
• Published: Germany 2001
• Subjects: Animals; Clinical Trials as Topic; Gene Expression Regulation - drug effects; Humans; Iodine - metabolism; Iodine Radioisotopes - therapeutic use; Retinoids - pharmacology; Retinoids - therapeutic use; RNA, Messenger - biosynthesis; Symporters - biosynthesis; Symporters - metabolism; Thyroid Neoplasms - metabolism; Thyroid Neoplasms - therapy; Tumor Cells, Cultured
• ISSN: 0947-7349
• DOI: 10.1055/s-2001-11017

Decrease or loss of iodide uptake, due to impaired expression and/or function of the sodium/iodide-symporter (NIS), is a major obstacle to the treatment of advanced thyroid carcinomas by radioiodide therapy. Several approaches are being evaluated to optimise or restore sufficient iodide transport in those cases, among them retinoid therapy. Retinoids with their growth-inhibiting and differentiation-inducing properties have been repeatedly used for treatment and chemoprevention of various cancers. In thyroid carcinoma cell lines they trigger changes in gene expression that may be interpreted as partial redifferentiation. Especially, they stimulate NIS mRNA expression and iodide uptake in human follicular thyroid carcinoma cells. Moreover, they also increase NIS expression and function in human mammary tumour cells. In a clinical pilot study to evaluate the feasibility of retinoid redifferentiation in the case of otherwise untreatable thyroid cancers, 21 of 50 patients showed an increase of radioiodide uptake after 5 weeks. This indicates that increasing NIS activity and radioiodide uptake by retinoic acid redifferentiation may be a therapeutic alternative for thyroid cancers refractory to other therapeutic modalities and probably also for mammary cancer.