Studies on the specific pathway of energy metabolism held in tumor cells and their application on the development of anti-tumor drugs

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Previously, we found that type II hexokinase is predominantly expressed in malignant tumor cells synchronized with the expression of type 1 glucose transporter and concluded the possible formation of atypical pathway of energy metabolism in tumor cells. In this research project, we focused on this atypical pathway of energy metabolism, we tried to characterize it and to develop new anti-tumor drugs. The obtained findings are follows :1) we isolated and characterized the promoter region of the gene encoding type II hexokinase (ref.1)2) we examined the effects of various culture couditions on the steady state transcript level of type II hexokinase and found a possible regulation of the transcript level of this enzyme by oxygen concentration (not yet published)3) to clarify the structural and functional features of this enzyme, we developed several chimera proteins between type II and type IV enzymes, and characterized their fouctional features (ref.4)4) to know the functional features of mitochondria-bound hexokinase, we isolated tumor mitochondria and examined the preference of the membrane bound hexokinase for ATP molecules synthesized by various systems. As a result, mitochondria-bound hexokinase was found to use preferentially the ATP synthesized by oxidative phosphorylation (ref.4)