BMC cancer · 2005
Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene.
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Presta Ivan, Arturi Franco, Ferretti Elisabetta, Mattei Tiziana, Scarpelli Daniela, Tosi Emanuele, Scipioni Angela, Celano Marilena, Gulino Alberto, Filetti Sebastiano, Russo Diego
Аннотация
BACKGROUND: Recovery of iodide uptake in thyroid cancer cells by means of obtaining the functional expression of the sodium/iodide symporter (NIS) represents an innovative strategy for the treatment of poorly differentiated thyroid cancer. However, the NIS gene expression alone is not always sufficient to restore radioiodine concentration ability in these tumour cells.
METHODS: In this study, the anaplastic thyroid carcinoma ARO cells were stably transfected with a Pax8 gene expression vector. A quantitative RT-PCR was performed to assess the thyroid specific gene expression in selected clones. The presence of NIS protein was detected by Western blot and localized by immunofluorescence. A iodide uptake assay was also performed to verify the functional effect of NIS induction and differentiation switch.
RESULTS: The clones overexpressing Pax8 showed the re-activation of several thyroid specific genes including NIS, Pendrin, Thyroglobulin, TPO and TTF1. In ARO-Pax8 clones NIS protein was also localized both in cell cytoplasm and membrane. Thus, the ability to uptake the radioiodine was partially restored, associated to a high rate of efflux. In addition, ARO cells expressing Pax8 presented a lower rate of cell growth.
CONCLUSION: These finding demonstrate that induction of Pax8 expression may determine a re-differentiation of thyroid cancer cells, including a partial recovery of iodide uptake, fundamental requisite for a radioiodine-based therapeutic approach for thyroid tumours.
METHODS: In this study, the anaplastic thyroid carcinoma ARO cells were stably transfected with a Pax8 gene expression vector. A quantitative RT-PCR was performed to assess the thyroid specific gene expression in selected clones. The presence of NIS protein was detected by Western blot and localized by immunofluorescence. A iodide uptake assay was also performed to verify the functional effect of NIS induction and differentiation switch.
RESULTS: The clones overexpressing Pax8 showed the re-activation of several thyroid specific genes including NIS, Pendrin, Thyroglobulin, TPO and TTF1. In ARO-Pax8 clones NIS protein was also localized both in cell cytoplasm and membrane. Thus, the ability to uptake the radioiodine was partially restored, associated to a high rate of efflux. In addition, ARO cells expressing Pax8 presented a lower rate of cell growth.
CONCLUSION: These finding demonstrate that induction of Pax8 expression may determine a re-differentiation of thyroid cancer cells, including a partial recovery of iodide uptake, fundamental requisite for a radioiodine-based therapeutic approach for thyroid tumours.
Предметные рубрики MeSH
Blotting, WesternCell Line, TumorCell ProliferationCytoplasmDNA PrimersGene Expression Regulation, NeoplasticGenetic VectorsHumansIodidesIodine RadioisotopesMembrane Transport ProteinsMicroscopy, FluorescencePAX8 Transcription FactorPaired Box Transcription FactorsPlasmidsRNARNA, MessengerRecombinant ProteinsReverse Transcriptase Polymerase Chain ReactionSulfate TransportersSymportersThymus GlandThyroglobulinThyroid NeoplasmsTranscription, GeneticTransfectionSodium-Iodide Symporters