Species- and cell type-specific requirements for cellular transformation

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—...

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Bibliographic Details
Published in:Cancer cell 2004-08, Vol.6 (2), p.171-183
Main Authors: Rangarajan, Annapoorni, Hong, Sue J., Gifford, Annie, Weinberg, Robert A.
Format: Article
Language:English
Subjects:
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
ral Guanine Nucleotide Exchange Factor - metabolism
Retinoblastoma Protein - metabolism
Signal Transduction
Simian virus 40
Species Specificity
Telomerase - metabolism
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2004.07.009