There is considerable debate regarding the accuracy of mouse models for human cancer. A prominent example is the spectrum of tumors associated with oncogenic Ras in humans which often differs from those in mouse models. In the Aug 15 issue of Genes & Development (N. M. Hamad et al., Genes Dev Vol. 16 No. 16, pp. 2045-2057), the group of Christopher M. Counter shows that oncogenic Ras may transform murine and human cells by distinct mechanisms.
Mutated and constitutively activated forms of Ras are found in 30% of all human cancers and the involvement of aberrant Ras activation in oncogenesis has been underscored in numerous studies. From these studies, several downstream effectors and mediators of Ras-transforming activity have been identified with Raf serine/threonine kinases generally being the most potent at transforming murine cells. However, the group of C. M. Counter now finds that the RalGEF, and not the Raf pathway, is sufficient for Ras transformation in human cells. These findings not only highlight the value of dissecting the signaling pathways of oncoproteins in human cells. With RalGEF playing probably a key role in Ras-mediated human oncogenesis, the RalGEF-signaling pathway may also represent a promising target in the development of anticancer drugs, the authors suggest.
Christopher M. Counter
Departments of Pharmacology and Cancer Biology and Radiation Biology
Duke University Medical Center
Durham, NC 27710, USA
Message posted by: Ulrike Sattler
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