Loss of function of PTEN alters the relationship between glucose concentration and cell proliferation, increases glycolysis, and sensitizes cells to 2-deoxyglucose

PTEN loss of function enhances proliferation, but effects on cellular energy metabolism are less well characterized. We used an inducible PTEN expression vector in a PTEN-null glioma cell line to examine this issue. While proliferation of PTEN-positive cells was insensitive to increases in glucose concentration beyond 2.5 mM, PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to ∼10 mM, coinciding with a shift to glycolysis and “glucose addiction”. This demonstrates that the impact of loss of function of PTEN is modified by glucose concentration, and may be relevant to epidemiologic results linking hyperglycemia to cancer risk and cancer mortality.