| Regulation of uptake of 18F-FDG by a follicular human thyroid cancer cell line with mutation-activated K-ras. | |
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MedLine Citation:
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PMID: 19652218 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Olaf Prante; Simone Maschauer; Valerie Fremont; Julia Reinfelder; Robert Stoehr; Mariusz Szkudlinski; Bruce Weintraub; Arndt Hartmann; Torsten Kuwert |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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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:
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Created Date: 2009-08-04 Completed Date: 2009-09-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: United States |
Other Details:
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Languages: eng Pagination: 1364-70 Citation Subset: IM |
Affiliation:
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Laboratory of Molecular Imaging, Clinic of Nuclear Medicine, Friedrich-Alexander University, Erlangen, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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