Document Detail


Regulation of uptake of 18F-FDG by a follicular human thyroid cancer cell line with mutation-activated K-ras.
MedLine Citation:
PMID:  19652218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Dedifferentiation of thyroid carcinoma is accompanied by increased accumulation of the PET tracer (18)F-FDG. The molecular mechanisms responsible for this phenomenon are poorly understood. Therefore, we studied the regulation of (18)F-FDG uptake by the human follicular thyroid carcinoma cell line ML-1 and the as-yet-unknown oncogene expression of that cell line. The data obtained in ML-1 were compared with those of a well-differentiated thyroid cell line of rat origin (FRTL-5). METHODS: The expression of the thyroid-stimulating hormone (TSH) receptor was investigated by immunocytochemistry, and the expression of the glucose transporters (GLUTs) was determined by Western blotting. Mutation analysis of ML-1 was performed for K-ras codons 12 and 13. The effect of TSH on intracellular cAMP levels was determined by a competitive enzyme immunoassay. Cells were incubated with (18)F-FDG (0.5-1.0 MBq/mL) for 1 h, and tracer uptake was related to protein concentration. The effects of bovine TSH, the cAMP analog (Bu)(2)cAMP, and the phosphatidylinositol-3-kinase (PI3-kinase) inhibitor LY294002 on (18)F-FDG uptake were investigated. RESULTS: The TSH receptor was present in both cell lines. FRTL-5 clearly expressed GLUT-1 and also GLUT-4. In ML-1 only, the expression of GLUT-3 was detected. TSH and (Bu)(2)cAMP had a significant effect on (18)F-FDG uptake or GLUT-1 expression in FRTL-5, but not in ML-1 cells. PI3-kinase inhibition by LY294002 downregulated (18)F-FDG uptake in FRTL-5 by 58% +/- 9% (n = 6) and in ML-1 by 26% +/- 5% (n = 42, both P < 0.05). Mutation analysis of ML-1 cells revealed a Gly12Ser point mutation at codon 12 of the K-ras gene. CONCLUSION: (18)F-FDG uptake in the thyroid carcinoma cell line ML-1 is no longer regulated by TSH or cAMP or mediated by GLUT-1. However, in this cell line, this variable is still governed to some extent by PI3-kinase located downstream to the constitutively active K-ras in the Ras-PI3-kinase-Akt pathway. These data suggest that increases in (18)F-FDG uptake in thyroid carcinomas observed in vivo by PET may reflect activation of intracellular signal transduction cascades by oncogenes.
Authors:
Olaf Prante; Simone Maschauer; Valerie Fremont; Julia Reinfelder; Robert Stoehr; Mariusz Szkudlinski; Bruce Weintraub; Arndt Hartmann; Torsten Kuwert
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of nuclear medicine : official publication, Society of Nuclear Medicine     Volume:  50     ISSN:  0161-5505     ISO Abbreviation:  J. Nucl. Med.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-04     Completed Date:  2009-09-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217410     Medline TA:  J Nucl Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1364-70     Citation Subset:  IM    
Affiliation:
Laboratory of Molecular Imaging, Clinic of Nuclear Medicine, Friedrich-Alexander University, Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenoma / genetics,  metabolism*,  radionuclide imaging
Cell Line, Tumor
Enzyme Activation
Fluorodeoxyglucose F18 / diagnostic use,  pharmacokinetics*
Gene Expression Regulation, Neoplastic
Humans
Mutation / genetics
Radiopharmaceuticals / diagnostic use,  pharmacokinetics
Thyroid Neoplasms / genetics,  metabolism*,  radionuclide imaging*
ras Proteins / genetics,  metabolism*
Chemical
Reg. No./Substance:
0/Radiopharmaceuticals; 63503-12-8/Fluorodeoxyglucose F18; EC 3.6.5.2/ras Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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