Multimodality optical imaging and 18F-FDG uptake in wild-type p53-containing and p53-null human colon tumor xenografts.
During tumor development a switch to glycolytic metabolism known as the Warburg effect may provide cancer cells with a survival advantage and may also provide a therapeutic opportunity. A number of signals contribute to aerobic glycolysis including those mediated by HIF-1, c-Myc, Akt and Hexokinase. Recent studies have implicated the p53 tumor suppressor as a negative regulator of this switch. Using inducible p53 gene silencing in bioluminescent tumor xenografts we initially observed qualitatively similar levels of FDG uptake by PET small animal imaging in wild-type p53-expressing tumor xenografts and p53 gene-silenced xenografts. We further evaluated glucose uptake using FDG-PET/CT fusion imaging of green and red fluorescently-labeled wild-type and p53-null human colon tumor xenografts. Our results demonstrate that the wild-type p53-expressing tumor xenografts exhibit high levels of glucose uptake, similar to those observed in p53-null tumor xenografts, by quantitative PET imaging indicative of the glycolytic switch. Thus p53 function is not sufficient to suppress glucose uptake in cells and tumors that could theoretically support aerobic glycolysis.
Wang
Shulin
S
Department of Medicine (Hematology/Oncology), The Institute for Translational Medicine and Therapeutics, and Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Mintz
Akiva
A
Mochizuki
Kenjiro
K
Dorsey
Jay F
JF
Ackermann
Joseph M
JM
Alavi
Abass
A
El-Deiry
Wafik S
WS
D000332:Aerobiosis / Q000235:genetics; D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000032:analysis; D005947:Glucose / Q000032:analysis / Q000378:metabolism*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D019275:Radiopharmaceuticals; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18; D005947:Glucose