In vivo, basal membrane GLUT1 is upregulated over gestation, increased in diabetic pregnancy, and decreased in chronic hypoxia, while microvillous membrane GLUT1 is unaffected.
Recent studies have shown that GLUT1 and GLUT3 are both expressed in chondrocytes and their HIF-1alpha-mediated transcription may be dually stimulated in response to hypoxia and low glucose conditions which in turn promote anaerobic glycolysis in favor of oxidative phosphorylation.
In contrast to BeWo cells, hypoxia produced minimal increases in GLUT1 expression in explants; however, treatment with MG-132 did upregulate syncytial basal membrane GLUT1.
Significant coexpression of GLUT-1, Bcl-xL, and Bax could point to cooperation of these regulatory proteins in elimination due to irreversible injury, adaptation to hypoxia, reduction of further damage, and survival of colorectal cancer cells.
The present observations support that upregulation of HIF-1 alpha and its downstream targets GLUT1 and SDF-1 in colorectal adenomas and carcinomas may be due to hypoxia, in close interaction with an active phosphatidylinositol 3-kinases-AKT-mTOR pathway.