Glucose catabolism in cancer cells: regulation of the Type II hexokinase promoter by glucose and cyclic AMP.
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.
Rempel
A
A
Department of Biological Chemistry, John Hopkins University, School of Medicine, Baltimore, MD 21205-2185, USA.
Mathupala
S P
SP
Perdersen
P L
PL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006601:Hexoses / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D008356:Mannoheptulose / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D015398:Signal Transduction; D013449:Sulfonamides; D014162:Transfection; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D006601:Hexoses; D007546:Isoquinolines; D013449:Sulfonamides; D005576:Colforsin; D003994:Bucladesine; D008356:Mannoheptulose; D000242:Cyclic AMP; D006593:Hexokinase; D005947:Glucose; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D015056:1-Methyl-3-isobutylxanthine