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Deciphering the pathways leading to the enhancement of NIS transcription in thyroid tissue
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The sodium-iodide symporter (NIS) is expressed in the basolateral membrane of thyroid follicular cells and transports iodide into its interior. Its expression in thyroid cancers allows the use of radioactive iodine (RAI) as a therapeutic tool. Unfortunately, a significant proportion of patients lose the ability to uptake RAI due mainly to impairment of NIS function, without effective therapeutic alternatives.
Our main purpose was to extend the analysis of the impact of the PI3K/Akt/mTOR and NF-κB oncogenic signalling pathways on NIS expression. In an attempt to achieve that goal we first determined if the activation of the canonical NF-κB pathway, induced by the tumour necrosis factor alpha (TNF-α), affects NIS transcriptional regulation. Next, we also evaluated the effect of simultaneous inhibition of PI3K and mTOR.
This study pointed to a role of NF-κB on the down-regulation of NIS mRNA expression by treatment with TNF-α and phorbol 12-myristate 13-acetate (PMA) in PCCL3 cells. In the K1 cell line, which has very poor expression of NIS and a constitutively active PI3K pathway, we were able to restore NIS expression upon its inhibition.
The extended knowledge of these pathways involved in the regulation of NIS will be relevant for the development of therapies for the enhancement of iodide uptake efficiency in RAI refractory thyroid carcinomas.
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Sodium iodide symporter Thyroid carcinoma Radioactive iodine PI3K/Akt/mTOR NF-κB