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Título

Telomerase-driven expression of the sodium iodide symporter (NIS) for in vivo radioiodide treatment of cancer: A new broad-spectrum NIS-mediated antitumor approach

AutorRiesco-Eizaguirre, Garcilaso CSIC ORCID; Vieja, Antonio de la CSIC ORCID; Rodríguez, Irene; Miranda, Soledad CSIC; Martín-Duque, Pilar; Vassaux, Georges; Santisteban, Pilar CSIC ORCID
Palabras claveMedullary-thyroid cancer
Adenocarcinoma cell-line
Targeted radiotherapy
Reverse-transcriptase
Transport defect
Gene-expression
Na/i symporter
Fecha de publicación1-sep-2011
EditorEndocrine Society
CitaciónJournal of Clinical Endocrinology and Metabolism 96(9): E1435-E1443 (2011)
Resumen[Context]: Telomerase promoters (hTERT and hTR) are useful for transcriptional targeting in gene therapy models of cancer. Telomerase-driven expression of the sodium iodide symporter (NIS) in tumor cells has been successfully used as a reporter gene in vivo using positron emission tomography (PET) imaging. [Objective]: The aim of this study was to investigate the NIS-mediated therapeutic effect of telomerase promoters in a wide variety of human cancer cell lines. [Design and Methods]: Promoter fragments from either hTERT or hTR were used to drive the expression of NIS in cell lines derived from melanoma (M14), breast (MDA-MB-231), colon (HT-29), lung (H460), ovarian (OVCAR-3), and thyroid (TPC-1) carcinomas. Iodide uptake assays, protein immunodetection, and clonigenic assays were used to confirm NIS functional expression and the (131)I-mediated cytopathic effect. Tumor xenografts in mice were infected with hTERT and hTR and then treated using radioiodide. [Results]: Both promoters were selectively active in cancer cells that were effectively killed by exposure to (131)I. One single dose of 1 mCi (131)I markedly suppressed tumor growth of melanoma-derived tumor xenografts compared with controls. This effect was more modest in colon cancer-derived xenografts in part due to the reduced infectivity and the tumor cystic nature. The therapeutic effect of hTR promoter was found to be stronger than that of hTERT promoter. [Conclusions]: These results demonstrate that telomerase-driven expression of NIS could potentially have applications for 131I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated 131I therapy of melanoma tumors in vivo.
Versión del editorhttp://dx.doi.org/10.1210/jc.2010-2373
URIhttp://hdl.handle.net/10261/40153
DOI10.1210/jc.2010-2373
ISSN0021-972X
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