Deregulated simultaneous expression of multiple glucose transporter isoforms in malignant cells and tissues

To evaluate the molecular and functional characteristics of upregulated glucose uptake in malignant cells, the expression of four glucose transporter (Glut) isoforms as well as glucose transport were determined in benign and malignant cell lines and tissues. In vivo distribution of Glut proteins was examined by immunocytochemistry in 30 breast cancer samples. In comparison with benign controls upregulation of Glut 1 mRNA and Glut 3 mRNA was shown. Glut 2 mRNA could not be detected. Glut 4 mRNA was found in various malignant cell lines in contrast to the physiological restriction of Glut 4 to terminally differentiated muscle and fat cells. While Glut 3 protein was not detectable in non-neuronal tissues, the degree of overexpression of Glut 1 and 4 corresponded to the expression level of the respective mRNAs. 57% of the breast cancer tissues showed positivity for Glut 1, 43% for Glut 4. Functional integrity of Glut 4 was demonstrated by preserved insulin-responsiveness. In cell lines, glucose transport activity was positively correlated with proliferation rate. Enhanced translocation of Glut 4 to the plasma membrane in correlation with high Ki-67 positivity in tissues pointed to the same association in vivo. C-myc overexpression had no detectable influence on Glut expression. In conclusion, malignant cells demonstrate quantitative as well qualitative changes of Glut expression and activity. Alteration of differentiation-adapted transcription and expression of cell-specific Gluts may represent a part of the transformation process and contribute to tumor progression.