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The role of MDM2 and MDM4 in breast cancer development and prevention
Sue Haupt1,†,*, Reshma Vijayakumaran1,2,†, Panimaya Jeffreena Miranda1,2, Andrew Burgess3,4,Elgene Lim3,4, and Ygal Haupt1,2,5,6
1 Tumour Suppression Laboratory, Peter MacCallum Cancer Centre, Melbourne 3000, Australia
2 Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne 3000, Australia
3 The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia
4 St. Vincent’s Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2010, Australia
5 Department of Pathology, The University of Melbourne, Parkville, Victoria 3010, Australia
6 Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
† These authors contributed equally to this review *Correspondence to:Sue Haupt, E-mail: sue.haupt@petermac.org
J Mol Cell Biol, Volume 9, Issue 1, February 2017, Pages 53-61  https://doi.org/10.1093/jmcb/mjx007
Keyword:  MDM2, MDM4, TP53, p53, breast cancer

The major cause of death from breast cancer is not the primary tumour, but relapsing, drug-resistant, metastatic disease. Identifying factors that contribute to aggressive cancer offers important leads for therapy. Inherent defence against carcinogens depends on the individual molecular make-up of each person. Important molecular determinants of these responses are under the control of the mouse double minute (MDM) family: comprised of the proteins MDM2 and MDM4. In normal, healthy adult cells, the MDM family functions to critically regulate measured, cellular responses to stress and subsequent recovery. Proper function of the MDM family is vital for normal breast development, but also for preserving genomic fidelity. The MDM family members are best characterized for their negative regulation of the major tumour suppressor p53 to modulate stress responses. Their impact on other cellular regulators is emerging. Inappropriately elevated protein levels of the MDM family are highly associated with an increased risk of cancer incidence. Exploration of the MDM family members as cancer therapeutic targets is relevant for designing tailored anti-cancer treatments, but successful approaches must strategically consider the impact on both the target cancer and adjacent healthy cells and tissues. This review focuses on recent findings pertaining to the role of the MDM family in normal and malignant breast cells.