Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts.
Science
; 275(5306): 1649-52, 1997 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-9054359
ABSTRACT
NIH 3T3 fibroblasts stably transformed with a constitutively active isoform of p21(Ras), H-RasV12 (v-H-Ras or EJ-Ras), produced large amounts of the reactive oxygen species superoxide (.O2-). .O2- production was suppressed by the expression of dominant negative isoforms of Ras or Rac1, as well as by treatment with a farnesyltransferase inhibitor or with diphenylene iodonium, a flavoprotein inhibitor. The mitogenic activity of cells expressing H-RasV12 was inhibited by treatment with the chemical antioxidant N-acetyl-L-cysteine. Mitogen-activated protein kinase (MAPK) activity was decreased and c-Jun N-terminal kinase (JNK) was not activated in H-RasV12-transformed cells. Thus, H-RasV12-induced transformation can lead to the production of .O2- through one or more pathways involving a flavoprotein and Rac1. The implication of a reactive oxygen species, probably .O2-, as a mediator of Ras-induced cell cycle progression independent of MAPK and JNK suggests a possible mechanism for the effects of antioxidants against Ras-induced cellular transformation.
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Banco de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
Transformación Celular Neoplásica
/
Proteínas Proto-Oncogénicas p21(ras)
/
Genes ras
/
Especies Reactivas de Oxígeno
/
Superóxidos
/
Proteínas Quinasas Activadas por Mitógenos
Límite:
Animals
Idioma:
En
Año:
1997
Tipo del documento:
Article