TY - JOUR
T1 - Species- and cell type-specific requirements for cellular transformation
AU - Rangarajan, Annapoorni
AU - Hong, Sue J.
AU - Gifford, Annie
AU - Weinberg, Robert A.
N1 - Funding Information:
We thank Drs. J. Downward and W.C. Hahn for reagents, S. Stewart and I. BenPorath for help with experiments, and C. Kuperwasser, R.S. Watnick, J. Yang, S.A. Mani, and A.E. Karnoub for useful discussions and help with preparing the manuscript. This work was supported by NIH/NCI grant 5 RO1CA78461 and Merck/MIT to R.A.W.; A.R. is currently supported by the US Army DOD BCRP Postdoctoral Traineeship Award #BC020806. We apologize to those colleagues whose work could not be cited due to space restrictions.
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2004.07.009
DO - 10.1016/j.ccr.2004.07.009
M3 - Article
C2 - 15324700
AN - SCOPUS:4344646902
SN - 1535-6108
VL - 6
SP - 171
EP - 183
JO - Cancer Cell
JF - Cancer Cell
IS - 2
ER -
