Kansara Maya, Berridge Michael V
Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
Anticancer Res. 2004 Jul-Aug;24(4):2503-10.
Increased glucose uptake is characteristic of many tumours and transformed cells and, consequently, glucose deprivation would be expected to differentially affect cancer cell survival and growth. In this study we investigated whether specific oncogenes sensitise cells to apoptosis induced by glucose deprivation.
Oncogene-transformed 32D cells were deprived of glucose with or without IL-3 and [3H]2-deoxyglucose uptake measured. Apoptosis was determined by AnnexinV/propidium iodide staining, cell cycle distribution was analysed and MYC expression determined by Western blotting.
v-Hras and to some extent v-src and v-abl enhanced apoptosis induced by glucose deprivation in the presence of IL-3 but attenuated apoptosis in its absence. In contrast, bcr-abl was highly protective against glucose deprivation-induced apoptosis for 72 hours in the presence and absence of IL-3, while bcl-2 was mildly protective in the presence of IL-3. With strongly transforming oncogenes, c-MYC expression correlated with cell sensitivity to apoptosis induced by glucose deprivation.
Oncogenes vary markedly in their ability to protect cells from apoptosis following glucose deprivation and, in some situations, promote apoptosis.
葡萄糖摄取增加是许多肿瘤和转化细胞的特征，因此，预计葡萄糖剥夺会对癌细胞的存活和生长产生不同影响。在本研究中，我们调查了特定癌基因是否使细胞对葡萄糖剥夺诱导的凋亡敏感。
在有或无白细胞介素-3（IL-3）的情况下，使癌基因转化的32D细胞缺乏葡萄糖，并测量[3H]2-脱氧葡萄糖摄取。通过膜联蛋白V/碘化丙啶染色确定凋亡，分析细胞周期分布，并通过蛋白质印迹法测定MYC表达。
v-Hras以及在一定程度上v-src和v-abl在有IL-3存在时增强了葡萄糖剥夺诱导的凋亡，但在无IL-3时减弱了凋亡。相反，在有和无IL-3的情况下，bcr-abl在72小时内对葡萄糖剥夺诱导的凋亡具有高度保护作用，而bcl-2在有IL-3时具有轻度保护作用。对于强转化癌基因，c-MYC表达与细胞对葡萄糖剥夺诱导的凋亡的敏感性相关。
癌基因在保护细胞免受葡萄糖剥夺后凋亡的能力上有显著差异，并且在某些情况下会促进凋亡。
