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 lar ge extent on the overexpression of hexokinase Type II. In a previous s tudy we isolated and sequenced the hepatoma Type II hexokinase promote r and showed that it is activated by glucose in the highly glycolytic AS-30D hepatoma cell line under study, but not activated in control he patocytes [Mathupala, S.P., Rempel, A. and Pedersen, P.L. (1995) J. Bi ol. Chem. 270, 16918-16925]. Here we report that the promoter of the h exokinase Type II gene is maximally activated by glucose at concentrat ions above 5 mM. Moreover, the data strongly suggest that glucose can act alone without requirement for metabolism. Also, glucose-mediated p romoter activation is markedly potentiated by cAMP. This response may serve as a strategy for cancer cells to maintain the hexokinase transc ription rate high to ensure an efficient glucose utilization even unde r conditions where carbohydrates are limiting.