Distinct Ras requirements

Tumors associated with oncogenic Ras in humans differ markedly from those in mice — which fail to form pancreatic, thyroid, or colon neoplasms — suggesting that the mechanism of Ras transformation may not be as universal as has been believed. In August 15 Genes & Development, Nesrin Hamad and colleagues at Duke University Medical Center, Durham, North Carolina, US, confirm that the route to Ras oncogenesis varies between mammalian cells (Genes Dev 2002, 16:2045-2057).

Hamad et al. evaluated the role of specific effectors in mediating oncogenic Ras transformation in both human and murine cells. They observed that the signaling pathway activated by H-Ras12V37G was sufficient for Ras-dependant transformation and necessary for tumor formation in human cells, and that RalGEFs were critical components of this process. They also noted that the two most critical effectors of Ras transformation of rodent fibroblasts were incapable, either alone or in combination, of causing transformation ...