Hemopoietic cell transformation is associated with failure to downregulate glucose uptake during the G2/M phase of the cell cycle.
Growth factors and cytokines initiate multiple signal transduction pathways that lead to cell survival, cell cycle progression or differentiation. A common feature of these pathways is increased cellular metabolism and glucose uptake. Furthermore, the energy requirements of many cancers and transformed cell lines are met by constitutive upregulation of glucose uptake. Relationships among transforming events, glucose uptake and cell cycle progression are not well understood. Here we investigated the regulation of glucose transport during the cell cycle of growth factor-dependent 32D cells, primary T-cells, src-transformed 32D cells and Jurkat cells. Cells were enriched in the G1, S and G2/M phases of the cell cycle, and glucose transporter expression and 2-deoxyglucose uptake were measured. Glucose transporter expression increased with cell volume as cells progressed through the cell cycle. Growth factor-dependent 32D cells and T-lymphocytes were characterised by increased 2-deoxyglucose uptake from G1 to S and reduced uptake at G2/M, with the highest specific activity of transporters in the S phase. In contrast, src-transformed 32D cells and Jurkat cells showed increased 2-deoxyglucose uptake from S to G2/M, with the highest glucose transporter specific activity in G2/M. Our results show that glucose transport is regulated in a cell cycle-dependent manner and suggest that this regulation may be altered in transformed cells.
Kansara
Maya
M
Malaghan Institute of Medical Research, Wellington School of Medicine, PO Box 7060, South Wellington, New Zealand.
Berridge
Michael V
MV
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism / Q000493:pharmacokinetics; D015536:Down-Regulation / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology*
D009004:Monosaccharide Transport Proteins; D003847:Deoxyglucose; D005947:Glucose