Kinetics of iodide uptake and efflux in various human thyroid cancer cells by expressing sodium iodide symporter gene via a recombinant adenovirus.
We evaluated the potential of radioiodide therapy in human sodium iodide symporter (hNIS)-defective thyroid cancer cells via exogenous hNIS expression. Three human thyroid cancer cells (ARO, FRO and NPA) of different origin were transduced by a recombinant adenovirus encoding hNIS expression cassette (Rad-hNIS). The cells were efficiently transduced by a recombinant adenovirus in a virus dose-dependent manner. Consequently, the hNIS protein could be readily detected by Western blot analysis 48-h post-infection at 10 infectious virus particles per cell. These hNIS-transduced cells actively transported iodide into the cytoplasm at the level of 11635.3, 61571.6, and 19367.5 pmoles/10(6) cells in ARO, FRO, and NPA, respectively. However, a significant amount of iodide was eluted to an iodide-free media within 60 min in all the cell lines. RT-PCR analysis revealed that the expression of genes related to iodide trapping (Tg, TSHR and TPO) was dramatically downregulated in these cells. The present study indicates that functional hNIS can be efficiently expressed and is responsible for active transport of iodide in hNIS-negative human thyroid cancer cells by a recombinant adenovirus. However, the human thyroid cancer cells, along with downregulation of iodide metabolism-related gene expression, lose the ability to maintain iodide. Therefore, these kinetic characteristics of iodide uptake and efflux may limit the therapeutic potential of hNIS/radioiodide-based treatment following exogenous hNIS expression in human thyroid cancer.
Lee
Won Woo
WW
Department of Microbiology, University of Ulsan College of Medicine, Songpa, PO Box 145, Seoul, Korea.
Lee
Boyoung
B
Kim
Sung Jin
SJ
Jin
Jungsun
J
Moon
Dae Hyuk
DH
Lee
Heuiran
H
D000256:Adenoviridae / Q000235:genetics*; D004274:DNA, Recombinant; D003673:Defective Viruses; D015870:Gene Expression; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007700:Kinetics; D012333:RNA, Messenger / Q000032:analysis; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012974:Sodium Iodide / Q000493:pharmacokinetics*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099209:Sodium-Iodide Symporters
D004274:DNA, Recombinant; D007453:Iodide Peroxidase; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D012974:Sodium Iodide; D027981:Symporters; D000099209:Sodium-Iodide Symporters