Species- and cell type-specific requirements for cellular transformation

Cancer Cell. 2004 Aug;6(2):171-83. doi: 10.1016/j.ccr.2004.07.009.


Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tumorigenic conversion of normal murine fibroblasts, while perturbation of six pathways-involving p53, pRb, PP2A, telomerase, Raf, and Ral-GEFs-is needed for human fibroblasts. Cell type-specific differences also exist in the requirements for tumorigenic transformation: immortalized human fibroblasts require the activation of Raf and Ral-GEFs, human embryonic kidney cells require the activation of PI3K and Ral-GEFs, and human mammary epithelial cells require the activation of Raf, PI3K, and Ral-GEFs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Cellular Senescence
  • Enzyme Activation
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Humans
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoprotein Phosphatases / metabolism
  • Proto-Oncogene Proteins c-raf / metabolism
  • Retinoblastoma Protein / metabolism
  • Signal Transduction*
  • Simian virus 40
  • Species Specificity
  • Telomerase / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • ral Guanine Nucleotide Exchange Factor / metabolism


  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
  • ral Guanine Nucleotide Exchange Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-raf
  • Telomerase
  • Phosphoprotein Phosphatases