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Cell Death Dis. 2018 Jan 16;9(2):19. doi: 10.1038/s41419-017-0035-2.

MCL-1 is a prognostic indicator and drug target in breast cancer.

Author information

1
CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. Kirsteen.Campbell@glasgow.ac.uk.
2
Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK. Kirsteen.Campbell@glasgow.ac.uk.
3
CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
4
Tumour Microenvironment Team, The Institute of Cancer Research, Chester Beatty Laboratories, London, SW3 6JB, UK.
5
Applied Bioinformatics of Cancer, University of Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, Edinburgh, EH4 2XR, UK.
6
Institute of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK.
7
CRUK Beatson Institute, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. k.blyth@beatson.gla.ac.uk.

Abstract

Analysis of publicly available genomic and gene expression data demonstrates that MCL1 expression is frequently elevated in breast cancer. Distinct from other pro-survival Bcl-2 family members, the short half-life of MCL-1 protein led us to investigate MCL-1 protein expression in a breast cancer tissue microarray and correlate this with clinical data. Here, we report associations between high MCL-1 and poor prognosis in specific subtypes of breast cancer including triple-negative breast cancer, an aggressive form that lacks targeted treatment options. Deletion of MCL-1 in the mammary epithelium of genetically engineered mice revealed an absolute requirement for MCL-1 in breast tumorigenesis. The clinical applicability of these findings was tested through a combination of approaches including knock-down or inhibition of MCL-1 to show triple-negative breast cancer cell line dependence on MCL-1 in vitro and in vivo. Our data demonstrate that high MCL-1 protein expression is associated with poor outcome in breast cancer and support the therapeutic targeting of MCL-1 in this disease.

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