Oncogenes modulate cell sensitivity to apoptosis induced by glucose deprivation.
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.


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.


CONCLUSIONS
Oncogenes vary markedly in their ability to protect cells from apoptosis following glucose deprivation and, in some situations, promote apoptosis.
Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
Maya
M
Kansara
Michael V
MV
Berridge
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D016313:Genes, abl / Q000502:physiology; D019254:Genes, bcl-2 / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D016391:Genes, src / Q000502:physiology; D005947:Glucose / Q000172:deficiency* / Q000493:pharmacokinetics; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D009857:Oncogenes / Q000502:physiology*
D007377:Interleukin-3; D003847:Deoxyglucose; D005947:Glucose