Gene expression profile associated with oncogenic ras-induced senescence, cell death, and transforming properties in human cells.
We developed inducible and constitutive expression systems of Ha-RasV12 in HEK 293 cells to examine early oncogenic RasV12 signaling. Inducible expression of oncogenic Ras-triggered growth arrest, early senescence, and later apoptosis. Gene expression profile analysis revealed early Ras proliferation and cell cycle genes like c-fos, cyclin E, cdk2, cell-cell contact, and signaling like integrin a6, MEK5, and free radical signaling genes, like proline oxidase. Therefore, Ras-mediated signaling is a fine regulated process both positively and negatively influencing cell cycle, senescence, and apoptosis pathways. Novel early RAS-target genes could be potentially exploited in cancer diagnostics and therapeutics.
Moumtzi
Sophy S
SS
Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, Athens, 116 35 Greece.
Roberts
Michael L
ML
Joyce
Tobias
T
Evangelidou
Maria
M
Probert
Lesley
L
Frillingos
Stathis
S
Fotsis
Theodore
T
Pintzas
Alexander
A
D017209:Apoptosis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016922:Cellular Senescence / Q000235:genetics*; D004789:Enzyme Activation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013997:Time Factors; D014162:Transfection; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D018797:Cell Cycle Proteins; D020928:Mitogen-Activated Protein Kinases; D018631:ras Proteins