| Project/Area Number |
05557112
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
医薬分子機能学
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| Research Institution | University of Tokushima |
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Principal Investigator |
TERADA Hiroshi Faculty of Pharmaceutical Sciences, University of Tokushima, Professor, 薬学部, 教授 (00035544)
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| Co-Investigator(Kenkyū-buntansha) |
HORI Hitoshi Faculty of Engineering, Associate Professor, 工学部, 助教授 (90119008)
SHINOHARA Yasuo Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60226157)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥11,800,000 (Direct Cost: ¥11,800,000)
Fiscal Year 1994: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1993: ¥8,700,000 (Direct Cost: ¥8,700,000)
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| Keywords | Hexokinase / Tumor cells / Anti-tumor drug / Sugar metabolism / がん細胞株 / 遺伝子構造 |
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| Research Abstract |
We found that the steady state transcript level of type II hexokinase was specifically and remarkably elevated in rat tumor cell lines. In this study, we tried to establish a new strategy for the development of anti-tumor drugs and obtained following results.
1)We isolated the cDNA fragment encoding human type II hexokinase and analyzed its transcript level by Northern blotting. As a result, we found that the transcript level of the type II hexokinase is elevated not only in rat hepatoma cell line, but also in human tumor cell line, HepG2.
2)We isolated the gene encoding the type II hexokinase and characterized its structual features. As a result, we found a region which seems to be responsible for the enhanced expression of this gene in tumor cells.
3)We think that hexokinase increases its activity by receving ATP from the ADP/ATP carrier exist in the inner mitochondrial membrane. Thus, we exaimed structure and function of this carrier by measuring the reactivities of cystein residues exist in this carrier under the various conditions and succeeded to reveal the transport mechanism at a molecular level.
4)To find candidates of anti-tumor drug, we tried to establish the screening system of the specific inhibitor of the type II hexokinase. To obatin certain amount of this isozyme, we estabished a over-expression system of this enzyme in E.coli.
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