Publication
B-Raf-induced senescence in colorectal cells is antagonized by expression of tumour-related Rac1b
| dc.contributor.author | Henriques, Andreia | |
| dc.contributor.author | Barros, Patrícia | |
| dc.contributor.author | Moyer, Mary | |
| dc.contributor.author | Matos, Paulo | |
| dc.contributor.author | Jordan, Peter | |
| dc.date.accessioned | 2016-02-18T14:01:08Z | |
| dc.date.available | 2016-02-18T14:01:08Z | |
| dc.date.issued | 2015-08 | |
| dc.description.abstract | Mutations 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. | pt_PT |
| dc.identifier.uri | http://hdl.handle.net/10400.18/3403 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | no | pt_PT |
| dc.subject | Vias de Transdução de Sinal e Patologias Associadas | pt_PT |
| dc.subject | Colorectal Cancer | pt_PT |
| dc.subject | BRaf | pt_PT |
| dc.subject | Rac1b | pt_PT |
| dc.subject | Senescence | pt_PT |
| dc.title | B-Raf-induced senescence in colorectal cells is antagonized by expression of tumour-related Rac1b | pt_PT |
| dc.type | conference object | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Spetses, Grécia | pt_PT |
| oaire.citation.title | FEBS adavnced lecture course 'Molecular Mechanisms of Signal Transduction and Cancer', 16-24 August 2015 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | conferenceObject | pt_PT |