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PMID: 12183360 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Distinct requirements for Ras oncogenesis in human versus mouse cells.

Genes & development ·Vol. 16 ·No. 16 ·2002-08-15 ·Pages 2045-57

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

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.

MeSH Terms
Animals Cell Line Cell Transformation, Neoplastic Cells, Cultured Enzyme Activation Fibroblasts/metabolism Humans Immunoblotting MAP Kinase Signaling System Mice Neoplasms/metabolism Phosphatidylinositol 3-Kinases/metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Time Factors Tumor Cells, Cultured ral Guanine Nucleotide Exchange Factor/metabolism ras Proteins/metabolism,physiology
Chemicals
ral Guanine Nucleotide Exchange Factor Phosphatidylinositol 3-Kinases ras Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Hamad Nesrin M
Department of Pharmacology, Division of Neurology, Duke University Medical Center, Durham North Carolina 27710, USA.
Elconin Joel H
Karnoub Antoine E
Bai Wenli
Rich Jeremy N
Abraham Robert T
Der Channing J
Counter Christopher M
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.993902
Published
2002-08-15
Pages
2045-57
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC186434
Subset
IM
Grants
NCI NIH HHS · R01 CA069577 · United States
NINDS NIH HHS · NS02055 · United States
NCI NIH HHS · CA69577 · United States
NCI NIH HHS · CA094184 · United States
NCI NIH HHS · R01 CA082481 · United States
NCI NIH HHS · R01 CA094184 · United States
NCI NIH HHS · CA82481 · United States
External Links
PubMed source DOI: 10.1101/gad.993902 PMC Full Text View journal details
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