Department of Oncology, McGill University, Segal Cancer Centre, Jewish General Hospital, Montreal, QC, Canada H3T 1E2.
Cancer Lett. 2010 Mar 28;289(2):246-53. doi: 10.1016/j.canlet.2009.08.021. Epub 2009 Sep 9.
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.
PTEN 功能丧失增强了增殖,但对细胞能量代谢的影响还不太清楚。我们使用诱导型 PTEN 表达载体在 PTEN 缺失的神经胶质瘤细胞系中研究了这个问题。虽然 PTEN 阳性细胞的增殖对 2.5mM 以上的葡萄糖浓度增加不敏感,但 PTEN 缺失的细胞在正常生理范围内随着葡萄糖浓度的增加显著增加增殖,大约达到 10mM,同时发生糖酵解和“葡萄糖成瘾”。这表明 PTEN 功能丧失的影响受葡萄糖浓度的调节,这可能与将高血糖与癌症风险和癌症死亡率联系起来的流行病学结果有关。