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

在我们之前的研究中，我们发现II型己糖激酶的稳态转录水平在大鼠肿瘤细胞系AH130中特异性和显著增强。本研究首先，为了证实II型己糖激酶在肿瘤细胞中表达增强的普遍性，我们检测了II型己糖激酶在人肿瘤细胞系和转化细胞系中的转录水平。结果再次证实了II型己糖激酶在恶性肿瘤细胞中转录水平的增加。接下来，为了了解II型己糖激酶在肿瘤细胞中特异性增加的分子机制，我们进行了多次实验，得到了以下结果。1)为了了解II型己糖激酶在肿瘤细胞中转录激活的分子机制，我们分离了编码该己糖激酶同工酶基因的启动子区域，并对其结构特征和转录活性进行了表征。2)为了了解II型己糖激酶与其他己糖激酶同工酶的功能差异，我们检测了II型己糖激酶的功能特征。3)为了了解肿瘤细胞中观察到的II型己糖激酶分子与线粒体结合的生理意义，我们检测了与肿瘤线粒体结合的己糖激酶的功能特征。结果表明，氧化磷酸化产生的ATP比与肿瘤线粒体结合的己糖激酶在细胞质中产生的ATP更容易被利用。

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.