title: Hypoxia stimulates 18F-fluorodeoxyglucose uptake in breast cancer cells via hypoxia inducible factor-1 and AMP-activated protein kinase.
abstract: BACKGROUND
  Hypoxia can stimulate (18)F-fluorodeoxyglucose (FDG) uptake in cultured cells. A better understanding of the underlying molecular mechanism is required to determine the value of FDG for studying tumour hypoxia.
  
  
  METHODS
  The effect of hypoxia on FDG uptake, and key proteins involved in glucose transport and glycolysis, was studied in MCF7 and MDA231 breast cancer cell lines.
  
  
  RESULTS
  Hypoxia induced a dose- and time-dependent increase in FDG uptake. The FDG increase was transient, suggesting that FDG uptake is only likely to be increased by acute hypoxia (<24 h). Molecular analysis indicated that hypoxia upregulated glut1 and 6-phosphofructo-2-kinase, key proteins involved in regulating glucose transport and glycolysis, and that these changes were induced by Hypoxia-Inducible factor 1 (HIF1) upregulation and/or AMP-activated protein kinase activation.
  
  
  CONCLUSIONS
  FDG may provide useful information about the oxygenation status of cells in hypoxic regions where HIF1 upregulation is hypoxia-driven.
authors.affiliation: Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD.
authors.forename: Tim A D
authors.initials: TA
authors.lastname: Smith
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanda
authors.forename: Ian N
authors.initials: IN
authors.lastname: Fleming
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology*; D015687:Cell Hypoxia / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D061986:MCF-7 Cells
chemical_list: D051793:Hypoxia-Inducible Factor 1; D019788:Fluorodeoxyglucose F18; D004317:Doxorubicin; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: (18)F-Fluorodeoxyglucose; (18)F-Fluoromisonidazole; 6-phosphofructo-2-kinase; AMP-activated protein kinase; AMPK; DTT; Dithiothreitol; FDG; FMISO; Fluorodeoxyglucose; HIF1; HK2; Hexokinase 2; Hypoxia; Hypoxia-inducible factor 1; MDA231; MDAMB231; OMG; Oncology, Positron Emission Tomography; PBS; PET; PFK2; Phosphate buffered saline; Positron Emission Tomography; [(3)H]-o-methylglucose