Distinct requirements for Ras oncogenesis in human versus mouse cells.

Journal Article (Review)

The spectrum of tumors associated with oncogenic Ras in humans often differs from those in mice either treated with carcinogens or engineered to sporadically express oncogenic Ras, suggesting that the mechanism of Ras transformation may be different in humans. Ras stimulates primarily three main classes of effector proteins, Rafs, PI3-kinase, and RalGEFs, with Raf generally being the most potent at transforming murine cells. Using oncogenic Ras mutants that activate single effectors as well as constitutively active effectors, we find that the RalGEF, and not the Raf or PI3-kinase pathway, is sufficient for Ras transformation in human cells. Thus, oncogenic Ras may transform murine and human cells by distinct mechanisms, and the RalGEF pathway--previously deemed to play a secondary role in Ras transformation--could represent a new target for anti-cancer therapy.

Full Text

Duke Authors

Cited Authors

  • Hamad, NM; Elconin, JH; Karnoub, AE; Bai, W; Rich, JN; Abraham, RT; Der, CJ; Counter, CM

Published Date

  • August 15, 2002

Published In

Volume / Issue

  • 16 / 16

Start / End Page

  • 2045 - 2057

PubMed ID

  • 12183360

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.993902

Language

  • eng

Conference Location

  • United States