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BMC Cancer  2005 

Recovery of NIS expression in thyroid cancer cells by overexpression of Pax8 gene

DOI: 10.1186/1471-2407-5-80

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Abstract:

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.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.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.Thyroid tumours show a good long-term survival, but, when we consider the poorly differentiated histotypes and in particular the anaplastic carcinoma, the prognosis is very poor [1,2]. A major determinant of such an opposite behaviour is the lost ability to concentrate the radioiodine, used as very effective tool for diagnosis and treatment for both tumour remnants or distant metastases [3]. The loss of iodide uptake capacity in poorly differentiated thyroid carcinomas is mainly due to the reduced/lost functional expression of the sodium/iodide symporter (NIS), with a defect occurring mainly at gene expression level, but in some case involving post-transcriptional or other unknown alterations [4-7]. For this reason, many strategies have been used and are currently in progress in order to re-establish iodide uptake function by means of re-expressing the NIS in tumour cells. At present, two

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