https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27649 Wed 17 May 2017 11:47:32 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19023 V600E or MEK downregulated Noxa, whereas activation of MEK/ERK caused its upregulation. In addition, introduction of BRAF^V600E increased Noxa expression in melanocytes. Upregulation of Noxa was due to a transcriptional increase mediated by cAMP responsive element binding protein, activation of which was also increased by MEK/ERK signaling in melanoma cells. Significantly, Noxa appeared necessary for constitutive activation of autophagy, albeit at low levels, by MEK/ERK in melanoma cells. Furthermore, it was required for autophagy activation that delayed apoptosis in melanoma cells undergoing nutrient deprivation. These results reveal that oncogenic activation of MEK/ERK drives Noxa expression to promote autophagy, and suggest that Noxa has an indirect anti-apoptosis role in melanoma cells under nutrient starvation conditions.]]> Wed 11 Apr 2018 16:41:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15166 V600E melanoma cells to B-RAF inhibitors. Experimental Design: B-RAF^V600E melanoma cells were exposed to the B-RAF inhibitor PLX4720 for prolonged periods to select for cells resistant to apoptosis induced by the inhibitor. The resultant cells were analyzed for activation of extracellular signal regulated kinase (ERK), MAP/ERK kinase (MEK), and Akt, and related signals. Their roles in survival of the cells were also examined. Results: B-RAF^V600E melanoma cells selected for resistant to PLX4720-induced apoptosis retained the V600E mutation in B-RAF, and proliferated steadily in the presence of the inhibitor, albeit with slow growth rate. These cells displayed high levels of ERK activation, that is, at least in part, independent of the conventional RAF/MEK/ERK pathway, as MEK activation was low and inhibition of MEK did not significantly block activation of ERK. In contrast, extracellular signals appeared involved. This was associated with elevated activation of the phosphoinositide 3-kinase (PI3k)/Akt pathway and could be inhibited by serum starvation and inhibition of PI3k/Akt. Inhibition of MEK did not impact on survival of these cells, whereas serum starvation, inhibition of PI3K/Akt, and inhibition of ERK1/2 reduced their viability. Conclusions: These results indicate that sensitivity to induction of apoptosis may be a major determinant of long-term responses of B-RAF^V600E melanomas to specific inhibitors and suggest that rebound melanoma growth after initial treatment with the inhibitors may not be responsive to MEK inhibitors, but may be susceptible to inhibition of the PI3k/Akt pathway.]]> Wed 11 Apr 2018 16:15:39 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14866 Wed 11 Apr 2018 16:08:27 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15167 Wed 11 Apr 2018 16:01:18 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28314 Wed 11 Apr 2018 12:40:55 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20163 Sat 24 Mar 2018 07:51:41 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26954 Sat 24 Mar 2018 07:27:01 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:36768 Fri 03 Jul 2020 14:41:43 AEST ]]>