Molecular Biology of Glucose Transporter expressed in Brain Tumors

脑肿瘤中表达的葡萄糖转运蛋白的分子生物学

• 批准号: 04454366
• 负责人: NAGAMATSU Shinya
• 金额: $ 4.16万
• 依托单位: Kyorin Univ.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454366/
• 关键词: Brain tumor; glucose transporter; GLUT; PCR; cDNA cloning; Northern blot

There may be a close relationship between the growth rate of brain tumor and glucose metabolism, as clinical studies with positron emission tomography (PET) have demonstrated that cerebral metabolic ultilization of glucose is increased in brain tumors. Since the glucose is transported into the cell through a facilitated diffusion process, mediated by glucose transporter carrier protein (GLUT), GLUT must play an inportant role in glucose metabolism of a brain tumor. First of all, we have examined the expression of glucose transporter isoforms in human astrocytic tumors, and compared the levels of GLUT mRNA and protein with the histological grading of astrocytic tumor. Human astrocytic tumors expressed the mRNAs and proteins of GLUT1, GLUT3, and GLUT4. Among them, GLUT3 was the major isoform expressed in brain tumors. There was no correlation between the histological grading of human astrocytic tumor cells and the expression levels of glucose transporter. Second, we determined the relationship between the growth rate of C6 rat glioma cells, the glucose transport system, and glucose metabolism. Rat C6 glioma cells were subcloned to 4 different cell lines (CL1-CL4), where CL1 is growing slowly, and CL4 is rapidly growing. The levels of GLUT and uptake of glucose were markedly increased in CL4 compared to in CL1. Further, the concentrations of intracellular glucose and ATP also demonstrated the increased rate of glucose metabolism in the rapidly growing cells (CL4). These results suggest that the facilitative glucose transporter (GLUT) may be altered in astrocytic tumor cells and the growth rate of glioma cells is closely related to the glucose transport and glucose metabolism.

脑肿瘤的生长速度与葡萄糖代谢之间可能存在密切关系，正电子发射断层扫描（PET）的临床研究表明，脑肿瘤中葡萄糖的脑代谢利用增加。由于葡萄糖通过葡萄糖转运载体蛋白（GLUT）介导的易化扩散过程转运到细胞中，因此GLUT在脑肿瘤的葡萄糖代谢中起重要作用。首先，我们检测了葡萄糖转运蛋白亚型在人脑星形细胞肿瘤中的表达，并比较了GLUT mRNA和蛋白水平与星形细胞肿瘤的组织学分级之间的关系。人星形细胞肿瘤表达GLUT 1、GLUT 3和GLUT 4的mRNA和蛋白质。其中，GLUT 3是脑肿瘤中表达的主要亚型。星形细胞肿瘤细胞的组织学分级与葡萄糖转运蛋白的表达水平无相关性。其次，我们确定了C6大鼠胶质瘤细胞的生长速度，葡萄糖转运系统和葡萄糖代谢之间的关系。将大鼠C6神经胶质瘤细胞亚克隆至4种不同的细胞系（CL 1-CL 4），其中CL 1生长缓慢，而CL 4生长迅速。与CL 1相比，CL 4中的GLUT水平和葡萄糖摄取显著增加。此外，细胞内葡萄糖和ATP的浓度也证明了快速生长细胞（CL 4）中葡萄糖代谢速率的增加。提示星形胶质细胞肿瘤细胞中易化葡萄糖转运蛋白（GLUT）可能发生改变，胶质瘤细胞的生长速度与葡萄糖转运和糖代谢密切相关。

项目成果

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Watanabe,T.,Nagamatsu,S.,et al.：“大鼠视网膜中的 GLUT2 表达：位于 Muller 细胞顶端的定位。”

永松信達、中道洋子、佐和弘基: "脳タイプのグルコーストランスポーター" 生体の科学. 45. 32-37 (1994)

Nobutatsu Nagamatsu、Yoko Nakamichi、Hiroki Sawa：“脑型葡萄糖转运蛋白”《生物科学》45. 32-37 (1994)。

Nagamatsu S., et. al.: "Neuron-specific glucose transporter (NSGT) : CNS distribution of GLUT3 rat glucose transporter (RGT3) in rat central neurons." FEBS.Lett.334. 289-295 (1993)

Nagamatsu S.，等。

Nahamatsu S,Sawa H,Inoue N,Takeshima H,Nakamichi Y,Murakawa S,Hoshino T: "Effects of glucose on the brain specific GLUT3 and GLUT1 glucose trans porter genes in mouse brain and primary clutured neuron form rat embryo." Diabetes.41. 158- (1992)

Nahamatsu S、Sawa H、Inoue N、Takeshima H、Nakamichi Y、Murakawa S、Hoshino T：“葡萄糖对小鼠大脑和大鼠胚胎初级培养神经元中大脑特异性 GLUT3 和 GLUT1 葡萄糖转运蛋白基因的影响。”

永松 信哉,武島 英人,中道 洋子,板垣 英二,脇坂 晟,村川 章一郎,佐和 弘基,星野 孝夫: "マウスβTC3細胞における糖輸送担体遺伝子(GLUT1,3)及びマウスGLUT3の脳特異的発現" 分子糖尿病学. 3. 45-51 (1992)

Shinya Nagamatsu、Hideto Takeshima、Yoko Nakamichi、Eiji Itagaki、Akira Wakisaka、Shoichiro Murakawa、Hiroki Sawa、Takao Hoshino：“小鼠 βTC3 细胞中葡萄糖转运蛋白基因 (GLUT1, 3) 和小鼠 GLUT3 的脑特异性表达”分子糖尿病学 3。 45-51（1992）