Document Detail


Iodide uptake in human anaplastic thyroid carcinoma cells after transfer of the human thyroid peroxidase gene.
MedLine Citation:
PMID:  11383870     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human thyroperoxidase (hTPO) is critical for the accumulation of iodide in thyroid tissues. Poorly differentiated and anaplastic thyroid tumours which lack thyroid-specific gene expression fail to accumulate iodide and, therefore, do not respond to iodine-131 therapy. We consequently investigated whether transfer of the hTPO gene is sufficient to restore the iodide-trapping capacity in undifferentiated thyroid and non-thyroid tumour cells. The human anaplastic thyroid carcinoma cell lines C643 and SW1736, the rat Morris hepatoma cell line MH3924A and the rat papillary thyroid carcinoma cell line L2 were used as in vitro model systems. Employing a bicistronic retroviral vector based on the myeloproliferative sarcoma virus for the transfer of the hTPO and the neomycin resistance gene, the C643 cells and SW1736 cells were transfected while the L2 cells and MH3924A cells were infected with retroviral particles. Seven recombinant C643 and seven SW1736 cell lines as well as four recombinant L2 and four MH3924A cell lines were established by neomycin selection. They were studied for hTPO expression using an antibody-based luminescence kit, followed by determination of the enzyme activity in the guaiacol assay and of the iodide uptake capacity in the presence of Na125I. Genetically modified cell lines expressed up to 1,800 times more hTPO as compared to wild type tumour cells. The level of hTPO expression varied significantly between individual neomycin-resistant cell lines, suggesting that the recombinant retroviral DNA was integrated at different sites of the cellular genome. The accumulation of iodide, however, was not significantly enhanced in individual recombinant cell lines, irrespective of low or high hTPO expression. Moreover, there was no correlation between hTPO expression and enzyme activity in individual cell lines. The transduction of the hTPO gene per se is not sufficient to restore iodide trapping in non-iodide-concentrating tumour cells. Future studies will have to concentrate on the possible expression of enzymatically active proteins or the transfer of multiple genes involved in iodide trapping.
Authors:
U Haberkorn; A Altmann; S Jiang; I Morr; M Mahmut; M Eisenhut
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of nuclear medicine     Volume:  28     ISSN:  0340-6997     ISO Abbreviation:  Eur J Nucl Med     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-31     Completed Date:  2001-12-04     Revised Date:  2006-04-21    
Medline Journal Info:
Nlm Unique ID:  7606882     Medline TA:  Eur J Nucl Med     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  633-8     Citation Subset:  IM    
Affiliation:
Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg. Uwe_Haberkorn@med.uni-heidelberg.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma / genetics,  metabolism*,  radiotherapy
Drug Resistance / genetics
Genetic Vectors
Humans
Iodide Peroxidase / genetics*,  metabolism,  physiology
Iodine / metabolism*
Iodine Radioisotopes / therapeutic use
Liver Neoplasms, Experimental / metabolism
Neomycin / pharmacology
Rats
Retroviridae
Thyroglobulin / metabolism
Thyroid Neoplasms / genetics,  metabolism*,  radiotherapy
Transfection
Tumor Cells, Cultured / drug effects,  metabolism
Chemical
Reg. No./Substance:
0/Iodine Radioisotopes; 1404-04-2/Neomycin; 7553-56-2/Iodine; 9010-34-8/Thyroglobulin; EC 1.11.1.8/Iodide Peroxidase

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