C10

The responsiveness of the glucose transporter to extracellular stimuli in embryos is an extremely important mechanism for providing more substrates to cope with the increased cellular demand arising from growth, proliferation, and differentiation. Galectin-1 regulates a wide variety of processes in embryogenesis. However, the precise role of galecitn-1 on the glucose metabolism in mouse embryonic stem (ES) cells is not completely understood. Therefore, this study investigated the effect of galectin-1 on the 2-deoxyglucose (2-DG) uptake and its related signal cascades in mouse ES cells. Galectin-1 significantly increased the level of 2-DG uptake in a time- (≥ 8 hr) and dose- (≥ 0.01 ng/ml) dependent manner. Moreover, galectin-1 increased glucose transporter (GLUT)-1 mRNA and protein expression levels, which were inhibited by a disruption in transcription by actinomycin D and translation by the cycloheximide. Subsequently, the galectin-1-induced 2-DG uptake were attenuated by these inhibitors. In investigation of signal transduction involved in this process, galectin-1 increased intracellular Ca2+ concentration ([Ca2+]i) and the PKC activation, which induced p44/42 MAPKs phosphorylation. On the other hand, in case that galectin-1 activated PI3K/Akt pathway, p44/42 MAPKs was not involved in this process. Moreover, mTOR signal pathway was stimulated in response to galectin-1. In experiment to examine the relationship between each pathway, mTOR phosphorylation was blocked by the inhibition of Ca2+/PKC, p44/42 MAPKs, and PI3K/Akt pathways, respectively. Finally, galectin-1-induced the increase of GLUT-1 expression and 2-DG uptake were inhibited by blocking of Ca2+/PKC, p44/42 MAPKs, PI3K/Akt, and mTOR pathways. In conclusion, galectin-1 up-regulates glucose uptake through Ca2+/PKC, p44/42 MAPKs, PI3K/Akt, and mTOR pathways in mouse embryonic stem cells.
 Key words: Galectin-1, 2-deoxyglucose uptake, GLUT-1, mouse embryonic stem cells

First AACR Centennial Conference on Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

American Association for Cancer Research
2007