Maya Kansara1, Michael V Berridge. 1. Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
Abstract
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Oncogenes vary markedly in their ability to protect cells from apoptosis following glucose deprivation and, in some situations, promote apoptosis.
BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Oncogenes vary markedly in their ability to protect cells from apoptosis following glucose deprivation and, in some situations, promote apoptosis.
Authors: Michelle Helen Visagie; Thandi Vuyelwa Mqoco; Leon Liebenberg; Edward Henry Mathews; George Edward Mathews; Anna Margaretha Joubert Journal: Cell Biosci Date: 2015-07-08 Impact factor: 7.133