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The BH3-only protein Bim(L) overrides Bcl-2-mediated apoptosis resistance in melanoma cells

Item Type:Article
Title:The BH3-only protein Bim(L) overrides Bcl-2-mediated apoptosis resistance in melanoma cells
Creators Name:Ploetz, M. and Gillissen, B. and Quast, S.A. and Berger, A. and Daniel, P.T. and Eberle, J.
Abstract:Melanoma cells are characterized by apoptosis deficiency coinciding with reduced expression of the proapoptotic Bcl-2 protein Bim. An adenoviral vector was constructed with the Bim(L) cDNA controlled by an inducible promoter. Highly efficient apoptosis induction and abrogated cell proliferation was seen in melanoma cells upon Bim(L) overexpression. Loss of mitochondrial membrane potential, release of mitochondrial apoptogenic factors and caspase-9 processing indicated the activation of mitochondrial apoptosis pathways. Bim(L) activated both Bax and Bak, as shown by siRNA knockdown and activation-specific antibodies. Of note, Bim(L) overrode the apoptosis blockade by Bcl-2 overexpression or by Bax/Bak single knockdown. The high efficacy correlated to Bim(L) interaction with all antiapoptotic Bcl-2 family members in melanoma cells, shown by co-immunoprecipitation analyses for Bcl-2, Bcl-x(L), Mcl-1 and Bcl-w. Thus, Bim(L) reveals an outstanding proapoptotic potential in melanoma cells, and strategies for its re-expression appear of interest. These have been reported for B-Raf inhibitors, and their efficacy may be partly attributed to Bim(L).
Keywords:Melanoma, Apoptosis, Bcl-2, Bim(L), Mitochondria
Source:Cancer Letters
ISSN:0304-3835
Publisher:Elsevier (The Netherlands)
Volume:335
Number:1
Page Range:100-108
Date:10 July 2013
Official Publication:https://doi.org/10.1016/j.canlet.2013.02.005
PubMed:View item in PubMed

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