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Deciphering the pathways leading to the enhancement of NIS transcription in thyroid tissue

datacite.subject.fosEngenharia e Tecnologia::Outras Engenharias e Tecnologiaspt_PT
dc.contributor.advisorSilva, Ana
dc.contributor.authorPaixão, Francisca Ventura
dc.date.accessioned2019-05-17T09:37:30Z
dc.date.available2022-05-06T00:30:38Z
dc.date.issued2019-05-06
dc.date.submitted2019
dc.description.abstractThe 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.pt_PT
dc.identifier.urihttp://hdl.handle.net/10362/69909
dc.language.isoengpt_PT
dc.subjectSodium iodide symporterpt_PT
dc.subjectThyroid carcinomapt_PT
dc.subjectRadioactive iodinept_PT
dc.subjectPI3K/Akt/mTORpt_PT
dc.subjectNF-κBpt_PT
dc.titleDeciphering the pathways leading to the enhancement of NIS transcription in thyroid tissuept_PT
dc.typemaster thesis
dspace.entity.typePublication
rcaap.rightsopenAccesspt_PT
rcaap.typemasterThesispt_PT
thesis.degree.nameGenética Molecular e Biomedicinapt_PT

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