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

FEBS Letters

Rempel, Annette¹  Pedersen, Peter L.¹  Mathupala, Saroj P.¹ 

[1] Department of Biological Chemistry, The Johns Hopkins University, School of Medicine, Baltimore, MD 21205-2185, USA

关键词: Cancer;    Type II hexokinase;    Glucose catabolism;    Cyclic AMP;    Protein kinase A;    Gene regulation;    2DOG;    2-deoxyglucose;    dbtcAMP;    dibutyryl cAMP;    IBMX;    3-isobutyl-1-methylxanthine;    3-OMetGlc;    3-O-methylglucose;    PKA;    protein kinase A;   

DOI  :  10.1016/0014-5793(96)00399-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown