Raf proteins are components of a conserved signaling pathway that regulates cellular responses to extracellular signals. In murine development, all Raf isozymes are indispensable for life and their disruption results in embryonic or perinatal lethality. However, many questions remain regarding the regulation and function of the Raf proteins. In particular, it was recently shown that B-Raf is mutated at a high frequency in melanoma and other human cancers. In order to further understand the consequences of activating B-Raf mutations in cell biology, we have developed and characterized melanoma cells lines in which B-raf expression can be abolished in a tetracycline-inducible fashion using a novel siRNA approach. Accordingly, using this knockdown strategy we have assessed the role of B-Raf(V600E) in cell and tumor growth in both in vitro and in vivo settings.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]