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

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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.