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Cell Cycle. 2004 Jun;3(6):715-7. Epub 2004 Jun 28.

The normal response to RAS: senescence or transformation?

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Program in Cancer Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.


Normal cells are thought to protect against transformation by undergoing a permanent cell cycle arrest, cellular senescence, in response to the expression of activated oncogenes such as RAS. We recently found that freshly established neonatal human fibroblasts are resistant to RAS-induced senescence. Moreover, extended passaging of normal fibroblasts leads to increased levels of the cyclin dependent kinase inhibitor p16 and sensitizes cells to senescence induced by RAS. These findings implicate exogenous stress as a necessary cofactor in RAS-induced senescence and demonstrate that RAS expression can promote some characteristics of transformation in the absence of other genetic changes.

[Indexed for MEDLINE]

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