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 2.5mM, PTEN-null cells significantly increased proliferation with increasing glucose concentration across the normal physiologic range to approximately 10mM, 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.
Blouin
Marie-José
MJ
Department of Oncology, McGill University, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada H3T 1E2. michael.pollak@mcgill.ca
Zhao
Yunhua
Y
Zakikhani
Mahvash
M
Algire
Carolyn
C
Piura
Esther
E
Pollak
Michael
M
D000963:Antimetabolites / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology*; D005434:Flow Cytometry; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D010101:Oxygen Consumption / Q000187:drug effects; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D003847:Deoxyglucose; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005947:Glucose