Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts.


Journal Article

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.

Full Text

Cited Authors

  • Irani, K; Xia, Y; Zweier, JL; Sollott, SJ; Der, CJ; Fearon, ER; Sundaresan, M; Finkel, T; Goldschmidt-Clermont, PJ

Published Date

  • March 1997

Published In

Volume / Issue

  • 275 / 5306

Start / End Page

  • 1649 - 1652

PubMed ID

  • 9054359

Pubmed Central ID

  • 9054359

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.275.5306.1649


  • eng