title: Telomerase-driven expression of the sodium iodide symporter (NIS) for in vivo radioiodide treatment of cancer: a new broad-spectrum NIS-mediated antitumor approach.
abstract: BACKGROUND
  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.
  
  
  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 (131)I therapy of a wide variety of cancers. Additionally, this is the first study to report NIS-mediated (131)I therapy of melanoma tumors in vivo.
authors.affiliation: Molecular Endocrinology, Instituto de Investigaciones Biomedicas, Arturo Duperier 4, Madrid, Spain 28029.
authors.forename: Garcilaso
authors.initials: G
authors.lastname: Riesco-Eizaguirre
authors.forename: Antonio
authors.initials: A
authors.lastname: De la Vieja
authors.forename: Irene
authors.initials: I
authors.lastname: Rodríguez
authors.forename: Soledad
authors.initials: S
authors.lastname: Miranda
authors.forename: Pilar
authors.initials: P
authors.lastname: Martín-Duque
authors.forename: Georges
authors.initials: G
authors.lastname: Vassaux
authors.forename: Pilar
authors.initials: P
authors.lastname: Santisteban
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D011401:Promoter Regions, Genetic; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D000099209:Sodium-Iodide Symporters
chemical_list: D007457:Iodine Radioisotopes; D027981:Symporters; D019098:Telomerase; D000099209:Sodium-Iodide Symporters