RT Journal Article SR Electronic T1 Tumor 18F-FDG Incorporation Is Enhanced by Attenuation of P53 Function in Breast Cancer Cells In Vitro JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1525 OP 1530 VO 47 IS 9 A1 Tim A.D. Smith A1 Rituka I. Sharma A1 Alastair M. Thompson A1 Fiona E.M. Paulin YR 2006 UL http://jnm.snmjournals.org/content/47/9/1525.abstract AB 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 18F-FDG detected using 18F-FDG PET has been associated with a poor prognosis. To determine whether high 18F-FDG uptake may be related to decreased expression of WT p53, we examined 18F-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. 18F-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. 18F-FDG uptake was increased in both clones expressing the dominant negative p53 constructs. Conclusion: These data suggest that abrogation of p53 in breast cancer is associated with specific changes in glucose metabolism detected by PET.