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Transposition of the thyroid iodide uptake and organification system in nonthyroid tumor cells by adenoviral vector-mediated gene transfers.

Abstract
Radioactive iodine (131I) is routinely used for the treatment of differentiated thyroid cancers. Attempts have been made to enlarge this therapeutic strategy to nonthyroid tumors by coupling radioactive iodide administration with transfer of the sodium iodide symporter (NIS) gene into target cells, for example with an adenoviral vector (AdNIS). Although efficient iodide uptake was achieved in the tumors treated with AdNIS, no therapeutic effect could be observed with 131I, most probably because the iodide retention time in the target cells was short. To circumvent this problem, we propose to organify the iodide taken up, as it occurs in the thyroid. We constructed a recombinant adenovirus encoding the human thyroperoxidase (TPO) gene under the control of the cytomegalovirus early promoter (AdTPO). Infection of nonthyroid tumor cells with this virus led to production of an enzymatically active protein. A significant increase in iodide organification could be observed in cells coinfected with both AdNIS and AdTPO in the presence of exogenous hydrogen peroxide. However, the levels of iodide organification obtained were too low to significantly increase the iodide retention time in the target cells.
AuthorsAnne Boland, Claire Magnon, Sebastiano Filetti, Jean-Michel Bidart, Martin Schlumberger, Patrice Yeh, Michel Perricaudet
JournalThyroid : official journal of the American Thyroid Association (Thyroid) Vol. 12 Issue 1 Pg. 19-26 (Jan 2002) ISSN: 1050-7256 [Print] United States
PMID11838726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Iodides
  • Iodine Radioisotopes
  • Recombinant Proteins
  • Symporters
  • sodium-iodide symporter
  • Hydrogen Peroxide
  • Iodide Peroxidase
Topics
  • Adenoviridae (genetics)
  • Animals
  • Biological Transport
  • Cell Line
  • Cytomegalovirus (genetics)
  • Gene Expression
  • Genetic Vectors
  • Humans
  • Hydrogen Peroxide (pharmacology)
  • Iodide Peroxidase (genetics, metabolism)
  • Iodides (metabolism)
  • Iodine Radioisotopes (metabolism)
  • Neoplasms (metabolism)
  • Promoter Regions, Genetic
  • Rats
  • Recombinant Proteins
  • Symporters (genetics)
  • Thyroid Gland (metabolism)
  • Transfection

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