Apoptosis induced by c-myc overexpression is dependent on growth conditions

Recent reports have suggested a causal link between the expression of the c-myc gene and ensuing cell death by apoptosis, particularly in cells prevented from dividing or after withdrawal of growth factors. In contrast, other studies have suggested that cells constitutively expressing c-myc are actually more resistant to cell death induced by some chemotherapeutic drugs that block cell division. We have examined the frequency of cell death in several Chinese hamster ovary cell lines that contain 20 to 30 copies of the human c-myc gene and that express high levels of human c-myc mRNA and protein. We found that constitutive c-myc expression in cells incubated at low density in medium containing 0.1% serum correlates with increased cell death due to apoptosis, as indicated by oligonucleosomal DNA fragmentation and a requirement for ongoing protein synthesis. However, apoptosis was not enhanced in these cells when they were blocked in cell division in the presence of serum, nor when grown at moderate to high density under low-serum conditions, despite their continued accumulation of high levels of c-Myc protein. Our results show that overexpression of c-Myc protein can promote cell death under some but not all conditions that block cell division and further suggest that c-Myc may accelerate but does not necessarily initiate apoptosis.