Signal transmission of carcinogenesis and tumorigenesis and formation of specific metabolic pathway in tumor cells.

癌变和肿瘤发生的信号传递以及肿瘤细胞内特定代谢途径的形成。

• 批准号: 10470496
• 负责人: TERADA Hiroshi
• 金额: $ 7.81万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470496/
• 关键词: energy metabolism; oxidative phosphorylation; mitochondria; glycolysis; antitumor drugs; type II hexokinase; type 1 glucose transporter

Previously, we found that the transcript level of type II hexokinase was remarkable in malignant tumor cells. However, the molecular mechanisms which cause such drastic changes in the transcript level of type II hexokinase in tumor cells is still unknown. Thus, in this study, we tried to understand how the expression of this gene is regulated in tumor cells. We obtained following results.1. We first explored under which condition the expression of type II hexokinase is remarkable. As a result, transcript level of type II hexokinase was remarkable when AH13O cells were grown in an abdominal cavity of rats. However, when this cell line was grown in culture dishes, the transcript level of type II hexokinase was remarkably lower than that observed with ascites cells. These results indicate that the transcript level of type II hexokinase could be changed accompanied by changes in culture conditions.2. To understand how such remarkable change is caused, we examined possible involvement of hypoxia and serum stimulation. As a result, gene expression of type II hexokinase was remarkably elevated by serum stimulation.Based on these results, we concluded that the metabolic pathway of sugar in tumor cells could be changed accompanied by changes in their growth conditions and that this change is mainly mediated by serum responsive factor.

以前，我们发现II型己糖激酶的转录水平在恶性肿瘤细胞中是显著的。然而，引起肿瘤细胞中II型己糖激酶转录水平如此剧烈变化的分子机制仍然未知。因此，在本研究中，我们试图了解该基因在肿瘤细胞中的表达是如何调节的。我们得到了如下结果：1.我们首先探索了在何种条件下II型己糖激酶的表达显著。结果，当AH13O细胞在大鼠腹腔中生长时，II型己糖激酶的转录水平显著。然而，当该细胞系在培养皿中生长时，II型己糖激酶的转录水平显著低于用腹水细胞观察到的水平。这些结果表明，随着培养条件的改变，II型己糖激酶的转录水平会发生变化.为了了解这种显着的变化是如何引起的，我们检查了可能涉及缺氧和血清刺激。结果表明，血清刺激可显著提高II型己糖激酶的基因表达，提示肿瘤细胞生长条件的改变可导致糖代谢途径的改变，而这种改变主要由血清反应因子介导。

项目成果

真島英司、寺田弘: "ATPはいかにして膜を透過するか:ループの協調的スウィングによるミトコンドリアADP/ATPキャリアーの機能発現" 生物物理. 38-6. 245-249 (1998)

Eiji Mashima、Hiroshi Terada：“ATP 如何渗透膜：通过环的协同摆动实现线粒体 ADP/ATP 载体的功能表达”，生物物理学 38-249（1998）。

M.Hashimoto et al.: "Irreversible extusion of the first loop facing the matrix bovine heart mitochondrial ADP/ATP carier by labeling the Cys56 residue with the SH-reagent methyl methanethiosulfonate"J.Biochem.. (印刷中).

M.Hashimoto 等人：“通过用 SH 试剂甲基硫代磺酸盐标记 Cys56 残基，对面向基质牛心线粒体 ADP/ATP 载体的第一个环进行不可逆的挤出”J.Biochem..（出版中）。

Y.shinohara and H.Terada: "Roles of hexokinase in aberrant sugar metabolism of tumor cells"Recent Research Development in Bioenergetics,Edited by S.G.Pandalai,Transworld Research NetWork,Trivandrum. (印刷中).

Y.shinohara 和 H.Terada：“己糖激酶在肿瘤细胞异常糖代谢中的作用”生物能量学的最新研究进展，由 S.G.Pandalai 编辑，Transworld Research Network，特里凡得琅（出版中）。

T. Daikoku, Y. Shinohara, A. Shima, N. Yamazaki and H. Terada: "Specific elevation of transcript levels of particular protein subtypes induced in brown adipose tissue by cold exposure"Biochim. Biophys. Acta. (in press).

T. Daikoku、Y. Shinohara、A. Shima、N. Yamazaki 和 H. Terada：“冷暴露导致棕色脂肪组织中特定蛋白质亚型转录水平的特异性升高”Biochim。

Y. Shinohara and H. Terada: "Roles of hexokinase in aberrant sugar metabolism of tumor cells"Recent Research Development In Bioenergetics Edited by S.G. Pandalai, Transworld Research NetWork, Trivandrum.. (in press).

Y. Shinohara 和 H. Terada：“己糖激酶在肿瘤细胞异常糖代谢中的作用”生物能量学的最新研究进展，由 S.G. Pandalai 编辑，Transworld Research Network，Trivandrum..（正在印刷中）。