Henriques, AndreiaBarros, PatríciaMoyer, MaryMatos, PauloJordan, Peter2016-02-182016-02-182015-08http://hdl.handle.net/10400.18/3403Mutations in the BRAF oncogene have been identified as a tumour-initiating genetic event in mainly melanoma, thyroid and colon cancer, resulting in an initial proliferative stimulus that is followed by a growth arrest period known as oncogene-induced senescence (OIS). It remains unknown what triggers subsequent escape from OIS to allow further tumour progression. A previous analysis revealed that around 80% of colorectal tumours carrying a mutation in BRAF also overexpress splice variant Rac1b. We used normal NCM460 colonocytes as a model to express oncogenic B-Raf-V600E in the presence or absence of co-transfected Rac1b and analysed the effect on expression the senescence marker β-galactosidase and of the cell-cycle inhibitors p14, p15 and p21. We provide evidence that co-expression of splice variant Rac1b counteracts B-Raf-induced senescence. When oncogenic B-Raf-V600E was expressed we observed the induction of the senescence marker β-galactosidase and of the cell-cycle inhibitors p14, p15 and p21. Upon co-expression of splice variant Rac1b, the B-Raf-induced senescence was relieved and expression of the cell-cycle inhibitor proteins downregulated. Our data indicate the selection for increased Rac1b expression as one potential mechanism by which colorectal tumour cells can escape from B-Raf-induced OIS.engVias de Transdução de Sinal e Patologias AssociadasColorectal CancerBRafRac1bSenescenceconference object