Abstract P6-01-05: Enhancement of18F-FDG uptake and glycolysis by epidermal growth factor via PI3K activation in T47D breast cancer cells

Abstract

Abstract It is well known that the binding of epidermal growth factor (EGF) to EGF receptors (EGFR) stimulates proliferation of breast cancer cells via activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathways. There was a report that glucose consumption and lactate production were increased in MDA-MB-468 breast cancer cells following EGF exposure. However, the effect of EGF in enhancing glucose uptake and signaling pathways that are involved have not been clearly revealed. We thus investigated the role of EGF in stimulation of18F-FDG uptake in T47D breast cancer cells, and further elucidated the molecular mechanisms that are involved. Exposure of T47D cells to 100 ng/mL EGF for 24 h caused a substantial augmentation of18F-FDG uptake to even greater extents to 310.8% ± 30.1% of control cells (P < 0.001), and this effect of EGF showed dose- and time-dependency. Increased glucose uptake by EGF occurred through enhanced membrane GLUT-1 expression as well as hexokinase activity. Inhibition experiments with cycloheximide showed that the metabolic effect by EGF required new protein biosynthesis. Stimulation of glucose uptake by EGF was dependent on sufficient EGFR expression because18F-FDG uptake in MCF-7 cells weakly expressing EGFR was not affected by EGF treatment. Although EGF was also a stimulator of T47D cell proliferation (137.3 ± 7.3% of basal levels at 24 h, P < 0.001), the metabolic effect occurred in a manner that clearly preceded and surpassed the proliferative effect. EGF-stimulated proliferation was significantly inhibited by the EGFR inhibitor BIBX1382, the PI3K inhibitor LY294002 and the specific MAPK inhibitor PD98059. Unlike proliferation, the ability of EGF to augment18F-FDG uptake was found to be dependent on PI3K but not on MAPK activity. These findings yield the insight into our understanding of the role of EGF and the molecular basis that are involved in glucose metabolism of breast cancer cells. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-01-05.