Transposition of the thyroid iodide uptake and organification system in nonthyroid tumor cells by adenoviral vector-mediated gene transfers.
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.
Boland
Anne
A
UMR 1582 CNRS-IGR-Aventis, Institut Gustave Roussy, Villejuif, France.
Magnon
Claire
C
Filetti
Sebastiano
S
Bidart
Jean-Michel
JM
Schlumberger
Martin
M
Yeh
Patrice
P
Perricaudet
Michel
M
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D011994:Recombinant Proteins; D027981:Symporters / Q000235:genetics; D013961:Thyroid Gland / Q000378:metabolism*; D014162:Transfection; D000099209:Sodium-Iodide Symporters
D006861:Hydrogen Peroxide; D007453:Iodide Peroxidase; D007454:Iodides; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D027981:Symporters; D000099209:Sodium-Iodide Symporters