Induction of autophagy and inhibition of melanoma growth in vitro and in vivo by hyperactivation of oncogenic BRAF.

ABSTRACT: Activating mutations in NRAS and BRAF are found frequently in cutaneous melanomas. Because concurrent mutations of both BRAF and RAS are extremely rare, it is thought that transformation by RAS and BRAF occurs through a common mechanism. Also, there is evidence for a relationship of synthetic lethality between NRAS and BRAF oncogenes that leads to selection against cells with a hyperactive mitogen-activated protein kinase (MAPK) pathway. However, it is not known whether the hyperactivation of the MAPK pathway by overexpression of either oncogene alone could also inhibit melanoma tumorigenesis. Here, we show that in melanoma cells with oncogenic BRAF (mBRAF), high levels of mBRAF induce hyperactivation of ERK and senescence-like phenotype and trigger autophagy by inhibiting the mammalian ta

SUBMITTER: Maddodi N 

PROVIDER: S-EPMC2869390 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature