title: Prevention of v-Ha-Ras-dependent apoptosis by PDGF coordinates in phosphorylation of ERK and Akt.
abstract: In some v-Ha-ras-transfected cell lines, serum deprivation results in apoptosis. Clarification of the molecular mechanisms by which oncogenic Ras controls 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-deprived conditions. Ladders of cellular DNA were identified only when oncogenic ras was induced under serum-deprived conditions. Platelet-derived growth factor (PDGF) precluded DNA fragmentation of serum-deprived v-Ha-ras-transformed cells. Under serum-depleted conditions, the amounts of activated ERK and Akt decreased as compared with those under serum-containing conditions. The decreased levels of activated ERK and Akt were restored by the addition of PDGF. Inhibition of phosphorylated-ERK and Akt resulted in renewed susceptibility to cell death. These results indicate that failure of signal transduction of oncogenic Ras by the deficiency of growth factors such as PDGF causes v-Ha-Ras-dependent apoptosis.
authors.affiliation: School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba, 260-8670, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Arase
authors.forename: T
authors.initials: T
authors.lastname: Hiwasa
authors.forename: R
authors.initials: R
authors.lastname: Hasegawa
authors.forename: J
authors.initials: J
authors.lastname: Nomura
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: N
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D011905:Genes, ras; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014466:Ultraviolet Rays; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D005419:Flavonoids; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D003907:Dexamethasone; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin