Regulation of prostate cancer cell division by glucose

Previous studies have shown that rapid cell proliferation is associated wit h elevated glucose consumption. However, those studies did not establish wh ether glucose is required for prostate cancer cell proliferation or define the molecular mechanisms by which glucose regulates cell division. We addre ssed these issues by studying two metastatic human prostate cancer cell lin es: DU145, which is androgen independent and highly proliferative; and LNCa P, which is androgen dependent and relatively slow growing. We found that p roliferation of DU145 cells was significantly inhibited by reduction of glu cose in the medium to 0.5 g/L, which is half the physiologic concentration, whereas LNCaP cells grew at control rates even in the presence of only 0.0 5 g/L glucose. Glucose deprivation of DU145 cells caused a 90% reduction in DNA synthesis; a 10-20-fold reduction in cyclins D and E and CDK4 levels; and cell cycle arrest in G(0)-G(1). However, glucose deprivation did not ca use global inhibition of protein synthesis, since mutant p53 levels increas ed in glucose-deprived DU145 cells. This observed increase in mutant p53 le vels was not associated with a rise in p21 levels. Glucose deprivation of D U145 cells also led to apparent dephosphorylation of mutant retinoblastoma (RB) protein. We conclude that: 1) high levels of glucose consumption are r equired for rapid proliferation of androgen-independent prostate canter cel ls, 2) glucose may not be required for slow growth of androgen-dependent pr ostate cancer cells, and 3) glucose promotes passage of cells through early G(1) by increasing the expression of several key cell cycle regulatory pro teins that normally inhibit RE function. (C) 1999 Wiley-Liss, Inc.