Glucose catabolism in cancer cells: regulation of the Type II hexokinase promoter by glucose and cyclic AMP

FEBS Lett. 1996 May 6;385(3):233-7. doi: 10.1016/0014-5793(96)00399-7.


The increased glucose consumption of many tumor cells depends to a large extent on the overexpression of hexokinase Type II. In a previous study we isolated and sequenced the hepatoma Type II hexokinase promoter and showed that it is activated by glucose in the highly glycolytic AS-30D hepatoma cell line under study, but not activated in control hepatocytes [Mathupala, S.P., Rempel, A. and Pedersen, P.L. (1995) J. Biol. Chem. 270, 16918-16925]. Here we report that the promoter of the hexokinase Type II gene is maximally activated by glucose at concentrations above 5 mM. Moreover, the data strongly suggest that glucose can act alone without requirement for metabolism. Also, glucose-mediated promoter activation is markedly potentiated by cAMP. This response may serve as a strategy for cancer cells to maintain the hexokinase transcription rate high to ensure an efficient glucose utilization even under conditions where carbohydrates are limiting.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Bucladesine / pharmacology
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Neoplastic
  • Glucose / metabolism*
  • Glucose / pharmacology*
  • Hexokinase / antagonists & inhibitors
  • Hexokinase / genetics*
  • Hexokinase / metabolism
  • Hexoses / pharmacology
  • Isoquinolines / pharmacology
  • Liver Neoplasms, Experimental / enzymology*
  • Mannoheptulose / pharmacology
  • Promoter Regions, Genetic / drug effects*
  • Rats
  • Signal Transduction
  • Sulfonamides*
  • Transfection
  • Tumor Cells, Cultured


  • Enzyme Inhibitors
  • Hexoses
  • Isoquinolines
  • Sulfonamides
  • Colforsin
  • Bucladesine
  • Mannoheptulose
  • Cyclic AMP
  • Hexokinase
  • Glucose
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
  • 1-Methyl-3-isobutylxanthine