がん細胞の活発な増殖を担うII型ヘキソキナーゼの活性発現機構

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In our previous study, we found that the steady state transcript level of type II hexokinase was specifically and remarkably enhanced in rat tumor cell line, AH130. In this study, first of all, to confirm the universality of the enhanced expression of type II hexokinase in tumor cells, we examined its transcript levels in human tumor cell lines and transformed cell lines. As a result, increment in the transcript level of type II hexokinase in malignant tumor cells was reconfirmed. Next, to understand the molecular mechanisms in the specific increment of type II hexokinase in tumor cells, we carried out several experiments and obtained following results.1) To understand the molecular mechanism of the transcriptional activation of type II hexokinase in tumor cells, we isolated the promoter region of the gene encoding this hexokinase isozyme and characterized its structural feature and transcriptional activity.2) To know the functional difference between type II hexokinase and the other hexokinase isozymes, we examined the functional feature of type II hexokinase.3) To understand the physiological meaning of the binding of type II hexokinase molecule on mitochondria observed in tumor cells, we examined the functional characteristics of the hexokinase bound to tumor mitochondria. Results showed the preferential use of ATP generated by oxidative phosphorylation than that exist in cytosol by hexokinase bound to tumor mitochondria.