Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Transformation, Neoplastic*
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Cells, Cultured
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Cellular Senescence
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Enzyme Activation
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Fibroblasts / cytology
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Fibroblasts / physiology
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Humans
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Mice
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Mice, Nude
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Phosphatidylinositol 3-Kinases / metabolism
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Phosphoprotein Phosphatases / metabolism
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Proto-Oncogene Proteins c-raf / metabolism
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Retinoblastoma Protein / metabolism
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Signal Transduction*
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Simian virus 40
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Species Specificity
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Telomerase / metabolism
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Tumor Suppressor Protein p53 / metabolism
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ral Guanine Nucleotide Exchange Factor / metabolism
Substances
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Retinoblastoma Protein
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Tumor Suppressor Protein p53
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ral Guanine Nucleotide Exchange Factor
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-raf
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Telomerase
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Phosphoprotein Phosphatases