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Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer

Gene Therapy volume 12, pages 272–280 (2005)Cite this article

Abstract

We investigated the feasibility of using radioiodine therapy in colon carcinoma cells (HCT 116) following tumor-specific expression of the human sodium iodide symporter (hNIS) using the carcinoembryonic antigen (CEA) promoter. HCT 116 cells were stably transfected with an expression vector, in which hNIS cDNA has been coupled to a CEA promoter fragment. This promoter is responsible for tissue-specific expression of CEA in gastrointestinal tract epithelium, and has been shown to target therapeutic genes to colorectal cancer cells. Functional NIS expression was confirmed by iodide uptake assay, Western blot analysis, immunostaining and in vitro clonogenic assay. The stably transfected HCT 116 cells concentrated 125I about 10-fold in vitro without evidence of iodide organification. In contrast, transfection of control cancer cells without CEA expression did not result in iodide accumulation. Western blot analysis using a hNIS-specific antibody revealed a band of approximately 90 kDa. In addition, immunostaining of stably transfected HCT 116 cells revealed hNIS-specific membrane-associated immunoreactivity. In an in vitro clonogenic assay approximately 95% of stably transfected HCT 116 cells were killed by exposure to 131I, while only about 5% of NIS-negative control cells were killed. Further, using an adenovirus carrying the NIS gene linked to the CEA promoter, high levels of tumor-specific radioiodide accumulation were induced in HCT 116 cells. In conclusion, a therapeutic effect of 131I has been demonstrated in colon carcinoma cells following induction of tumor-specific iodide uptake activity by CEA promoter-directed NIS expression in vitro. This study demonstrates the potential of NIS as a therapeutic gene allowing radioiodine therapy of colon cancer following tumor-specific NIS gene transfer.

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Acknowledgements

We are grateful to Sissy M Jhiang, PhD, Department of Physiology, Ohio State University, Columbus, OH, USA, for supplying the full-length human NIS cDNA. This study was supported by grants to C Spitzweg (Sp 581/3-1, Sp 581/3-2) from the German Research Council (Deutsche Forschungsgemeinschaft, Bonn, Germany), and by the Mayo Foundation Prostate Cancer SPORE grant (CA91956) to JC Morris.

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Authors and Affiliations

  1. Department of Internal Medicine II, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany

    I V Scholz, N Cengic, K Maletz, B Göke & C Spitzweg

  2. Department of Endocrinology, Mayo Clinic, Rochester, MN, USA

    C H Baker, E R Bergert & J C Morris

  3. Molecular Medicine Program, Mayo Clinic, Rochester, MN, USA

    K J Harrington & R Vile

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  1. I V Scholz
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  2. N Cengic
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Scholz, I., Cengic, N., Baker, C. et al. Radioiodine therapy of colon cancer following tissue-specific sodium iodide symporter gene transfer. Gene Ther 12, 272–280 (2005). https://doi.org/10.1038/sj.gt.3302410

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