Expression and function of hexose transporters GLUT1, GLUT2, and GLUT5 in breast cancer—effects of hypoxia

作者: Ingrit Hamann , Daniel Krys , Darryl Glubrecht , Vincent Bouvet , Alison Marshall

DOI: 10.1096/FJ.201800360R

关键词:

摘要: Elevated growth in breast cancer (BC) activates hypoxia-inducible factor (HIF1α) and downstream, facilitative glucose transporter 1 (GLUT1), which can be visualized with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG). GLUT5 (fructose) GLUT2 (glucose/fructose) might provide alternative targets for BC imaging as to why effects of hypoxia on GLUT1/2/5 levels function were examined human models. HIF1α mRNA was analyzed patient biopsies. In MCF10A, MCF7, MDA-MB231 cells, [18F]FDG, 6-deoxy-6-[18F]fluoro-d-fructose (6-[18F]FDF) [18F]-fluoroazomycin arabinoside used radiotracer experiments, whereas real-time PCR protein determined via Western blot/immunohistochemistry. Positron emission tomography performed MCF7 tumor-bearing mice. Glucose/fructose/cytochalasin B reduced cellular 6-[18F]FDF uptake by 50%, indicating functional involvement GLUT2. With staining lower than GLUT1, revealed [18F]FDG [standardized value (SUV)6-[18F]FDF, 120 min 0.77 ± 0.06 vs. SUV[18F]FDG, 1.08 0.07] tumors blocked 20% cytochalasin after 10 min. Whereas correspondence between low, high detected all cell lines tumor Besides seems regulated under the molecular level. Additionally, results strongly support a fructose metabolism, possibly compensating weaker expression BC.-Hamann, I., Krys, D., Glubrecht, Bouvet, V., Marshall, A., Vos, L., Mackey, J. R., Wuest, M., F. Expression hexose transporters GLUT2, cancer-effects hypoxia.

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