Prevention of v-Ha-Ras-dependent apoptosis by PDGF coordinates in phosphorylation of ERK and Akt
| Autor: | Yoshiko Arase, Ritsuko Hasegawa, Takaki Hiwasa, Jun Nomura, Nobuo Suzuki, Hisao Ito |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
MAPK/ERK pathway
Programmed cell death Cell Survival Ultraviolet Rays Biophysics Apoptosis DNA Fragmentation Protein Serine-Threonine Kinases Transfection Biochemistry Culture Media Serum-Free Dexamethasone Cell Line Proto-Oncogene Proteins p21(ras) Anti-apoptotic Ras signalling cascade Proto-Oncogene Proteins Humans Enzyme Inhibitors Phosphorylation Molecular Biology Protein kinase B Flavonoids Platelet-Derived Growth Factor biology Cell Biology Embryo Mammalian Recombinant Proteins Cell biology Androstadienes Genes ras Cancer research biology.protein Signal transduction Mitogen-Activated Protein Kinases Wortmannin Proto-Oncogene Proteins c-akt Platelet-derived growth factor receptor |
| Zdroj: | Biochemical and biophysical research communications. 267(1) |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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