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Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non–small cell lung cancer

Abstract

Radioiodide is an effective therapy for thyroid cancer. This treatment modality exploits the thyroid-specific expression of the sodium iodide symporter ( NIS ) gene, which allows rapid internalization of iodide into thyroid cells. To test whether a similar treatment strategy could be exploited in nonthyroid malignancies, we transfected non–small cell lung cancer (NSCLC) cell lines with the NIS gene. Although the expression of NIS allowed significant radioiodide uptake in the transfected NSCLC cell lines, rapid radioiodide efflux limited tumor cell killing. Because thyroperoxidase ( TPO ) catalyzes iodination of proteins and subsequently causes iodide retention within thyroid cells, we hypothesized that coexpression of both NIS and TPO genes would overcome this deficiency. Our results show that transfection of NSCLC cells with both human NIS and TPO genes resulted in an increase in radioiodide uptake and retention and enhanced tumor cell apoptosis. These findings suggest that single gene therapy with only the NIS gene may have limited efficacy because of rapid efflux of radioiodide. In contrast, the combination of NIS and TPO gene transfer, with resulting TPO-mediated organification and intracellular retention of radioiodide, may lead to more effective tumor cell death. Thus, TPO could be used as a therapeutic strategy to enhance the NIS-based radioiodide concentrator gene therapy for locally advanced lung cancer. Cancer Gene Therapy (2001) 8, 612–618

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Acknowledgements

This work is supported by National Institutes of Health Specialized Program of Research Excellence in Lung Cancer IP50CA90388 (S.M.D.), R01 CA71818 (S.M.D.), R01 CA085686 (S.M.D.), R01 CA78654 (R.K.B.), Medical Research Funds from the Department of Veteran Affairs, the Research Enhancement Award Program in Cancer Gene Medicine, and the Tobacco-Related Disease Research Program of the University of California.

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Correspondence to Min Huang.

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Huang, M., Batra, R., Kogai, T. et al. Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non–small cell lung cancer. Cancer Gene Ther 8, 612–618 (2001). https://doi.org/10.1038/sj.cgt.7700354

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