Lookup NU author(s): Christopher McKee,
Dr David Hill,
Dr Chris Redfern,
Dr Jane Armstrong,
Professor Penny Lovat
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The Bcl-2 family member Mcl-1 is essential for melanoma survival; however, the influence of oncogenic BRAF signalling remains elusive. In this study, Mcl-1 splice variant expression was determined in a panel of melanoma cell lines in relation to BRAF mutational status. Mcl-1L mRNA expression was increased in melanoma cells compared with primary melanocytes with significantly increased mRNA and protein expression observed in BRAF(V600E) mutant melanoma cells. Although no change in Mcl-1S mRNA was observed, Mcl-1S protein expression also increased in BRAF mutant melanoma cells. Additionally, while over-expression of mutant BRAF(V600E) increased both Mcl-1L and Mcl-1S expression, inhibition of hyperactive BRAF signalling resulted in decreased Mcl-1L expression. These studies suggest that the regulation of Mcl-1 expression by BRAF signalling is increased by oncogenic activation of BRAF, revealing a mechanism of apoptotic resistance which may be overcome by the use of more specifically targeted Mcl-1 inhibitors.
Author(s): McKee CS, Hill DS, Redfern CPF, Armstrong JL, Lovat PE
Publication type: Article
Publication status: Published
Journal: Experimental Dermatology
Print publication date: 29/10/2013
ISSN (print): 0906-6705
ISSN (electronic): 1600-0625
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