Expression and function of hexose transporters GLUT1, GLUT2, and GLUT5 in breast cancer—effects of hypoxia
Bibliographic record
Abstract
ABSTRACT Elevated growth in breast cancer (BC) activates hypoxia‐inducible factor (HIF1a) and downstream, facilitative glucose transporter 1 (GLUT1), which can be visualized with 2‐deoxy‐2‐[ 18 F]fluoro‐ D ‐glucose ([ 18 F]FDG). GLUT5 (fructose) and GLUT2 (glucose/fructose) might provide alternative targets for BC imaging as to why effects of hypoxia on GLUT1/2/5 levels and function were examined in human BC models. GLUT1/2/5 and HIF1a mRNA was analyzed in BC patient biopsies. In MCF10A, MCF7, and MDA‐MB231 cells, [ 18 F]FDG, 6‐deoxy‐6‐[ 18 F]fluoro‐ D ‐ fructose (6‐[ 18 F]FDF) and [ 18 F]‐fluoroazomycin arabinoside were used in radiotracer experiments, whereas GLUT1/2/5 mRNA was analyzed with real‐time PCR and protein levels determined via Western blot/ immunohistochemistry. Positron emission tomography imaging was performed in MCF7 and MDA‐MB231 tumor‐bearing mice. Glucose/fructose/cytochalasin B reduced cellular 6‐[ 18 F]FDF uptake by 50%, indicating functional involvement of GLUT2. With GLUT5 staining lower than GLUT1, 6‐[ 18 F]FDF revealed lower uptake than [ 18 F]FDG [standardized uptake value (SUV) 6 _[ 18 F]FDF, 120 min 0.77 ± 0.06 vs. SUV [ 18 F ]FDF , 120 min 1.08 ± 0.07] in MDA‐MB231 tumors and was blocked by 20% with cytochalasin B after 10 min. Whereas correspondence between 6‐[ 18 F]FDF uptake and GLUT5 protein was low, high GLUT2 levels were detected in all cell lines and tumor models. Besides GLUT1, GLUT5 seems to be regulated under hypoxia on the molecular and functional level. Additionally, results strongly support a functional involvement of GLUT2 in fructose metabolism, possibly by compensating for the weaker expression and function of GLUT5 in BC.—Hamann, I., Krys, D., Glubrecht, D., Bouvet, V., Marshall, A., Vos, L., Mackey, J. R., Wuest, M., Wuest, F. Expression and function of hexose transporters GLUT1, GLUT2, and GLUT5 in breast cancer—effects of hypoxia. FASEB J. 32, 5104–5118 (2018). www.fasebj.org
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".