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Induction of the nuclear proto-oncogene c-fos by the phorbol ester TPA and v-H-Ras.
- Source :
-
Molecules and cells [Mol Cells] 2008 Nov 30; Vol. 26 (5), pp. 462-7. - Publication Year :
- 2008
-
Abstract
- TPA is known to cooperate with an activated Ras oncogene in the transformation of rodent fibroblasts, but the biochemical mechanisms responsible for this effect have not been established. In the present study we used c-fos promoter-luciferase constructs as reporters, in transient transfection assays, in NIH3T3 cells to assess the mechanism of this cooperation. We found a marked synergistic interaction between TPA and a transfected v-Ha-ras oncogene in the activation of c-fos promoter and SRE. SRE has binding sites for TCF and SRF. A dominant-negative Ras (ras-N17) inhibited the TPA-Ras synergy by blocking the PKC-MAPK-TCF pathway. Dominant-negative RhoA and Rac1 (but not Cdc42Hs) inhibited the TPA-Ras synergy by blocking the Ras-Rho-SRF signaling pathway. Constitutively active PKCalpha and PKCepsilon showed synergy with v-Ras. These results suggest that the activation of two distinct pathways such as Ras-Raf-ERK-TCF pathway and Rho-SRF pathway are responsible for the induction of c-fos by TPA and Ras in mitogenic signaling pathways.
- Subjects :
- Animals
COS Cells
Cell Nucleus drug effects
Chlorocebus aethiops
Enzyme Activation drug effects
Gene Expression Regulation drug effects
Mice
NIH 3T3 Cells
Oncogene Protein p21(ras) genetics
Protein Kinase C metabolism
Serum Response Element
rho GTP-Binding Proteins metabolism
Cell Nucleus genetics
Genes, ras
Oncogene Protein p21(ras) metabolism
Proto-Oncogene Proteins c-fos genetics
Proto-Oncogene Proteins c-fos metabolism
Tetradecanoylphorbol Acetate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1016-8478
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecules and cells
- Publication Type :
- Academic Journal
- Accession number :
- 18719353