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Distinct requirements for Ras oncogenesis in human versus mouse cells.

Publication ,  Journal Article
Hamad, NM; Elconin, JH; Karnoub, AE; Bai, W; Rich, JN; Abraham, RT; Der, CJ; Counter, CM
Published in: Genes Dev
August 15, 2002

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.

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

August 15, 2002

Volume

16

Issue

16

Start / End Page

2045 / 2057

Location

United States

Related Subject Headings

  • ras Proteins
  • ral Guanine Nucleotide Exchange Factor
  • Tumor Cells, Cultured
  • Time Factors
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Phosphatidylinositol 3-Kinases
  • Neoplasms
  • Mice
  • MAP Kinase Signaling System
 

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Hamad, N. M., Elconin, J. H., Karnoub, A. E., Bai, W., Rich, J. N., Abraham, R. T., … Counter, C. M. (2002). Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev, 16(16), 2045–2057. https://doi.org/10.1101/gad.993902
Hamad, Nesrin M., Joel H. Elconin, Antoine E. Karnoub, Wenli Bai, Jeremy N. Rich, Robert T. Abraham, Channing J. Der, and Christopher M. Counter. “Distinct requirements for Ras oncogenesis in human versus mouse cells.Genes Dev 16, no. 16 (August 15, 2002): 2045–57. https://doi.org/10.1101/gad.993902.
Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT, et al. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev. 2002 Aug 15;16(16):2045–57.
Hamad, Nesrin M., et al. “Distinct requirements for Ras oncogenesis in human versus mouse cells.Genes Dev, vol. 16, no. 16, Aug. 2002, pp. 2045–57. Pubmed, doi:10.1101/gad.993902.
Hamad NM, Elconin JH, Karnoub AE, Bai W, Rich JN, Abraham RT, Der CJ, Counter CM. Distinct requirements for Ras oncogenesis in human versus mouse cells. Genes Dev. 2002 Aug 15;16(16):2045–2057.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

August 15, 2002

Volume

16

Issue

16

Start / End Page

2045 / 2057

Location

United States

Related Subject Headings

  • ras Proteins
  • ral Guanine Nucleotide Exchange Factor
  • Tumor Cells, Cultured
  • Time Factors
  • Signal Transduction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Phosphatidylinositol 3-Kinases
  • Neoplasms
  • Mice
  • MAP Kinase Signaling System