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Oncogenic BRAF signalling increases Mcl-1 expression in cutaneous metastatic melanoma

Lookup NU author(s): Christopher McKee, Dr David Hill, Dr Chris Redfern, Dr Jane Armstrong, Professor Penny Lovat

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Abstract

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.


Publication metadata

Author(s): McKee CS, Hill DS, Redfern CPF, Armstrong JL, Lovat PE

Publication type: Article

Publication status: Published

Journal: Experimental Dermatology

Year: 2013

Volume: 22

Issue: 11

Pages: 767-769

Print publication date: 29/10/2013

ISSN (print): 0906-6705

ISSN (electronic): 1600-0625

Publisher: Wiley-Blackwell

URL: http://dx.doi.org/10.1111/exd.12254

DOI: 10.1111/exd.12254


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