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Title: Functional and genomic characterisation of a xenograft model system for the study of metastasis in triple-negative breast cancer.
Austin Authors: Johnstone, Cameron N ;Pattison, Andrew D;Gorringe, Kylie L;Harrison, Paul F;Powell, David R;Lock, Peter;Baloyan, David;Ernst, Matthias ;Stewart, Alastair G;Beilharz, Traude H;Anderson, Robin L 
Affiliation: Cancer Research Division, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australi
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia
Department of Pathology, University of Melbourne, Parkville, Victoria, Australia
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
Department of Pharmacology & Therapeutics, University of Melbourne, Parkville, Victoria, Australia
Monash Bioinformatics Platform, Monash University, Clayton, Victoria, Australia
LIMS Bioimaging Facility, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia
Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Issue Date: 30-Apr-2018 2018-05-10
Publication information: Disease models & mechanisms 2018; 11(5): dmm032250
Abstract: Triple-negative breast cancer represents 10-20% of all human ductal adenocarcinomas and has a poor prognosis relative to other subtypes. Hence, new molecular targets for therapeutic intervention are necessary. Analyses of panels of human or mouse cancer lines derived from the same individual that differ in their cellular phenotypes but not in genetic background have been instrumental in defining the molecular players that drive the various hallmarks of cancer.To determine the molecular regulators of metastasis in triple-negative breast cancer, we completed a rigorous in vitro and in vivo characterization of four populations of the MDA-MB-231 human breast cancer line ranging in aggressiveness from non-metastatic to spontaneously metastatic to lung, liver, spleen and lymph node. Single nucleotide polymorphism (SNP) array analyses and genome-wide mRNA expression profiles of tumour cells isolated from orthotopic mammary xenografts were compared among the four lines to define both cell autonomous pathways and genes associated with metastatic proclivity.Gene set enrichment analysis demonstrated an unexpected association between both ribosome biogenesis and mRNA metabolism and metastatic capacity. Differentially expressed genes or families of related genes were allocated to one of four categories, associated with either metastatic initiation (for example CTSC, ENG, BMP2), metastatic virulence (e.g. ADAMTS1, TIE1) metastatic suppression (e.g. CST1, CST2, CST4, CST6, SCNNA1, BMP4) or metastatic avirulence (e.g. CD74).Collectively, this model system based on MDA-MB-231 cells should be useful for the assessment of gene function in the metastatic cascade and also for the testing of novel experimental therapeutics for the treatment of triple-negative breast cancer.
DOI: 10.1242/dmm.032250
ORCID: 0000-0001-5681-2022
Journal: Disease models & mechanisms
PubMed URL: 29720474
Type: Journal Article
Subjects: Breast cancer
Mouse model
Appears in Collections:Journal articles

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