Proliferation and survival molecules implicated in the inhibition of BRAF pathway in thyroid cancer cells harbouring different genetic mutations

摘要: Thyroid carcinomas show a high prevalence of mutations in the oncogene BRAF which are inversely associated with RAS or RET/PTC oncogenic activation. The possibility using inhibitors on pathway as became an interesting therapeutic approach. In thyroid cancer cells target molecules, implicated cellular effects, mediated by inhibition not well established. order to fill this lack knowledge we studied proliferation and survival pathways molecules induced carcinoma cell lines harbouring distinct genetic backgrounds. Suppression (8505C, TPC1 C643) was achieved RNA interference (RNAi) for kinase inhibitor, sorafenib. Proliferation analysis performed BrdU incorporation apoptosis accessed TUNEL assay. Levels protein expression were analysed western-blot. Both RNAi sorafenib inhibited all independently background, mostly BRAFV600E mutation. mutated lead decrease ERK1/2 phosphorylation cyclin D1 levels increase p27Kip1. Specific mutation had no effect apoptosis. case treatment, showed due balance anti-apoptotic proteins Mcl-1 Bcl-2. Our results cells, namely those BRAFV600Emutation that signalling provides important signals. We have shown induces affecting Bcl-2 independent BRAF. These suggest may prove useful treatment carcinomas, particularly refractory conventional mutations.