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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Rangarajan A,Hong SJ,Gifford A,Weinberg RAdoi
10.1016/j.ccr.2004.07.009keywords:
subject
Has Abstractpub_date
2004-08-01 00:00:00pages
171-83issue
2eissn
1535-6108issn
1878-3686pii
S1535610804002053journal_volume
6pub_type
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