Prevention of v-Ha-ras-dependent apoptosis by PDGF coordinates in phosphorylation of ERK and Akt

In some v-Ha-ras-transfected cell lines, serum deprivation results in apopt osis, Clarification of the molecular mechanisms by which oncogenic Ras cont rols susceptibility to apoptosis may assist in the development of effective therapies against human cancer with oncogenic ras gene. In this report, we established a v-Ha-ras-transfected human fibroblast clone, R1. In R1 cells , induction of v-Ha-Ras enhanced susceptibility to cell death under serum-d eprived conditions. Ladders of cellular DNA were identified only when oncog enic ras was induced under serum-deprived conditions. Platelet-derived grow th factor (PDGF) precluded DNA fragmentation of serum-deprived v-Ha-ras-tra nsformed cells. Under serum-depleted conditions, the amounts of activated E RK and Akt decreased as compared with those under serum-containing conditio ns, The decreased levels of activated ERK and Akt were restored by the addi tion of PDGF., Inhibition of phosphorylated-ERK and Akt resulted in renewed susceptibility to cell death. These results indicate that failure of signa l transduction of oncogenic Ras by the deficiency of growth factors such as PDGF causes v-Ha-Ras-dependent apoptosis, (C) 2000 Academic Press.