Distinct requirements for Ras oncogenesis in human versus mouse cells.

Abstract:

: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.

journal_name

Genes Dev

journal_title

Genes & development

authors

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

doi

10.1101/gad.993902

subject

Has Abstract

pub_date

2002-08-15 00:00:00

pages

2045-57

issue

16

eissn

0890-9369

issn

1549-5477

journal_volume

16

pub_type

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