Molecular mechanisms for mammalian glucose transporter expression and its function associated with human tumorigenesis.

哺乳动物细胞对葡萄糖的摄取是由一种完整的膜蛋白葡萄糖转运蛋白介导的，葡萄糖转运蛋白是一种N-连接的糖蛋白，分子量约为50 kDa。我们之前已经在宫颈癌HeLa和正常成纤维细胞之间的杂交细胞中证明了葡萄糖转运蛋白1(GLUT1)的肿瘤相关糖基化改变，并增加了对D-葡萄糖的亲和力，正常成纤维细胞的致瘤性受11号染色体上一个假定的肿瘤抑制基因的控制。在本研究中，我们证明了从CGL1细胞分离的伽玛射线诱导的肿瘤形成突变(GIM)表达肿瘤相关表面抗原-肠道碱性磷酸酶(ALP)的GLUT1糖基化改变。相反，在伽马辐射的非致瘤对照细胞(CONS)中，GLUT1没有显示出这种变化。根据这种糖基化变化，Gim克隆对2-脱氧葡萄糖的亲和力比非致癌Con克隆增加了约2倍。这些结果进一步表明，GLUT1的糖基化变化与对D-葡萄糖亲和力的增加与这些人类细胞杂交细胞的致瘤性之间存在密切的相关性。我们还发现，在致癌的HeLa细胞杂交细胞中，质膜小窝结构的主要蛋白质组分小窝蛋白的表达大大减少。这些细胞膜变化和一个假定的肿瘤抑制基因之间的遗传联系正在调查中。

Glucose uptake in mammalian cells is mediated by an integral membrane protein, glucose transporter, which is an N-linked glycoprotein with molecular mass of about 50 kDa. We have previously demonstrated a tumor-associated glycosylation change in glucose transporter-1 (GLUT1) with increased affinity to D-glucose in human cell hybrids between a cervical carcinoma HeLa and normal fibroblasts, whose tumorigenicity is under the control of a putative tumor suppressor in chromosome 11. In this study, we demonstrated this glycosylation change in GLUT1 in gamma-ray-induced tumorigenic mutants (GIMs) isolated from CGL1 cells as expressing a tumor-associated surface antigen, intestinal alkaline phosphatase. In contrast, GLUT1 in the gamma-irradiated nontumorigenic control cells (CONs) did not show this alteration. In accordance with this glycosylation change, affinity to 2-deoxyglucose in the GIM clone was increased by about 2-fold when compared to the nontumorigenic CON clone. These results further suggest a close correlation between the glycosylation change in GLUT1 with increased affinity to D-glucose and tumorigenicity of these human cell hybrids. We also found that the expression of caveolin, a principal protein component of caveolae structure in the plasma membrane, is greatly reduced in tumorigenic HeLa cell hybrids. Genetic linkage between these membrane changes and a putative tumor suppressor gene is under investigation.