Tumor 18F-FDG incorporation is enhanced by attenuation of P53 function in breast cancer cells in vitro.
Mutations in the p53 gene, often resulting in loss of wild-type (WT) p53 expression, are found at high frequencies in several cancer types. High uptake of (18)F-FDG detected using (18)F-FDG PET has been associated with a poor prognosis. To determine whether high (18)F-FDG uptake may be related to decreased expression of WT p53, we examined (18)F-FDG uptake in cells transfected with dominant negative p53 constructs that abrogate WT p53 function.


METHODS
Two clones of MCF-7 breast cancer cells were stably transfected with a dominant negative p53 construct. (18)F-FDG uptake, hexokinase (HK) activity, and glucose transport were measured in each clone and in the control WT cells from which the clones had been derived. The expression of glucose transporters, HKs, and glucose-6-phosphatase was determined using microarray technology.


RESULTS
Microarray experiments revealed that glucose transporters 1, 8, and 10 were expressed in MCF-7 cells, whereas glucose-6-phosphatase was absent. HK I was the principal HK in MCF-7 cells but was not differentially expressed at the messenger RNA level in the dominant negative p53 clones, compared with WT cells. However, increased HK activity was observed in both dominant negative p53 clones, compared with WT MCF-7. (18)F-FDG uptake was increased in both clones expressing the dominant negative p53 constructs.


CONCLUSIONS
These data suggest that abrogation of p53 in breast cancer is associated with specific changes in glucose metabolism detected by PET.
Smith
Tim A D
TA
Department of Biomedical Physics, School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom. t.smith@biomed.abdn.ac.uk
Sharma
Rituka I
RI
Thompson
Alastair M
AM
Paulin
Fiona E M
FE
D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D008657:Metabolic Clearance Rate; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18