ePrints

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

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

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

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

Altmetrics

Share