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-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.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Annapoorni
A
Rangarajan
Sue J
SJ
Hong
Annie
A
Gifford
Robert A
RA
Weinberg
D000818:Animals; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D016922:Cellular Senescence; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction; D013539:Simian virus 40; D013045:Species Specificity; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020726:ral Guanine Nucleotide Exchange Factor / Q000378:metabolism
D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D020726:ral Guanine Nucleotide Exchange Factor; D019869:Phosphatidylinositol 3-Kinases; D019908:Proto-Oncogene Proteins c-raf; D019098:Telomerase; D010749:Phosphoprotein Phosphatases