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

Decrease or loss of iodide uptake, due to impaired expression and/or functi on of the sodium/iodide-symporter (NIS), is a major obstacle to the treatme nt of advanced thyroid carcinomas by radioiodide therapy. Several approache s are being evaluated to optimise or restore sufficient iodide transport in those cases, among them retinoid therapy. Retinoids with their growth-inhi biting and differentiation-inducing properties have been repeatedly used fo r treatment and chemoprevention of various cancers. In thyroid carcinoma ce ll 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, th ey also increase NIS expression and function in human mammary tumour cells. In a clinical pilot study to evaluate the feasibility of retinoid rediffer entiation in the case of otherwise untreatable thyroid cancers, 21 of 50 pa tients showed an increase of radioiodide uptake after 5 weeks. This indicat es that increasing NIS activity and radioiodide uptake by retinoic acid red ifferentiation may be a therapeutic alternative for thyroid cancers refract ory to other therapeutic modalities and probably also for mammary cancer.