Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/3424
Título: Expression of tumour-related Rac1b antagonizes B-Raf-induced senescence in colorectal cells
Autor: Henriques, Andreia FA
Barros, Patrícia
Moyer, Mary
Matos, Paulo
Jordan, Peter
Palavras-chave: Vias de Transdução de Sinal e Patologias Associadas
Cancro Coloretal
Rac1b
Signalling
Senescence
B-Raf
Colorectal Cancer
Tumor Progression
Data: 28-Dez-2015
Editora: Elsevier
Citação: Cancer Lett. 2015 Dec 28;369(2):368-75. doi: 10.1016/j.canlet.2015.08.027. Epub 2015 Sep 1
Resumo: Mutations in the BRAF oncogene have been identified as a tumor-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 tumor progression. A previous analysis revealed that around 80% of colorectal tumors 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 then analyzed the effect on expression of senescence markers. When oncogenic B-Raf-V600E was expressed we observed the induction of the senescence-associated β-galactosidase and of the cell-cycle inhibitors p14, p15 and p21 whereas proliferation marker Ki67 was suppressed. Upon co-expression of splice variant Rac1b, but not of Rac1, the B-Raf-induced senescence phenotype was reverted and expression of the cell-cycle inhibitors downregulated in a reactive oxygen-species dependent manner. We thus provide evidence that co-expression of splice variant Rac1b counteracts B-Raf-induced senescence, indicating the selection for increased Rac1b expression as one potential mechanism by which colorectal tumor cells can escape from B-Raf-induced OIS.
Peer review: yes
URI: http://hdl.handle.net/10400.18/3424
DOI: 10.1016/j.canlet.2015.08.027
ISSN: 0304-3835
Versão do Editor: http://www.sciencedirect.com/science/article/pii/S0304383515005686
Aparece nas colecções:DGH - Artigos em revistas internacionais

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