PT  - JOURNAL ARTICLE
AU  - Prante, Olaf
AU  - Maschauer, Simone
AU  - Fremont, Valerie
AU  - Reinfelder, Julia
AU  - Stoehr, Robert
AU  - Hartmann, Arndt
AU  - Szkudlinski, Mariusz
AU  - Weintraub, Bruce
AU  - Kuwert, Torsten
TI  - Regulation of uptake of FDG by a follicular human thyroid cancer cell line with mutational activated K-ras
DP  - 2009 May 01
TA  - Journal of Nuclear Medicine
PG  - 275--275
VI  - 50
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/50/supplement_2/275.short
4100  - http://jnm.snmjournals.org/content/50/supplement_2/275.full
SO  - J Nucl Med2009 May 01; 50
AB  - 275 Objectives The molecular mechanisms responsible for increased FDG uptake in dedifferentiated thyroid carcinoma are as yet poorly understood. We studied the regulation of FDG uptake by the human follicular thyroid carcinoma cell line ML-1 in comparison with that by the well-differentiated rat thyroid cell line FRTL-5. Methods ML-1 and FRTL-5 cells were cultured in the presence of hormones with or without 1 mU/ml TSH. The effect of TSH on intracellular cAMP was determined by a competitive enzyme immunoassay. Cells were incubated with 0.5–1.0 MBq/mL FDG for 1 h, studying the effect of bTSH (1 mU/mL), (Bu)2cAMP (1mM), and LY294002 (PI3K inhibitor). GLUT subtypes were determined by Western blot. Mutational analyses for K-ras and B-raf V600 were performed for ML-1 cells. Results TSH induced increased intracellular cAMP levels in both cell lines. TSH and (Bu)2cAMP produced increased FDG uptake as well as GLUT-1 expression in FRTL-5, whereas no effect in ML-1 cells was observed. LY294002 downregulated FDG uptake in FRTL-5 by 58±9% and in ML-1 by 26±5%. Mutational analysis of ML-1 cells revealed a Gly12Ser point mutation at codon 12 of K-ras. Conclusions FDG uptake in ML-1 cells is not regulated by TSH or cAMP, but still governed by PI3K located downstream to the constitutively active K-ras in the PI3K-Akt pathway. Increased FDG uptake in thyroid carcinomas observed in vivo by PET may therefore reflect activation of intracellular signal transduction cascades by oncogenes.