Journal article
MDM4 is a rational target for treating breast cancers with mutant p53
Panimaya Jeffreena Miranda, Daniel Buckley, Dinesh Raghu, Jia-Min B Pang, Elena A Takano, Reshma Vijayakumaran, Amina FAS Teunisse, Atara Posner, Tahlia Procter, Marco J Herold, Cristina Gamell, Jean-Christophe Marine, Stephen B Fox, Aart Jochemsen, Sue Haupt, Ygal Haupt
JOURNAL OF PATHOLOGY | WILEY | Published : 2017
DOI: 10.1002/path.4877
Abstract
Mutation of the key tumour suppressor p53 defines a transition in the progression towards aggressive and metastatic breast cancer (BC) with the poorest outcome. Specifically, the p53 mutation frequency exceeds 50% in triple-negative BC. Key regulators of mutant p53 that facilitate its oncogenic functions are potential therapeutic targets. We report here that the MDM4 protein is frequently abundant in the context of mutant p53 in basal-like BC samples. Importantly, we show that MDM4 plays a critical role in the proliferation of these BC cells. We demonstrate that conditional knockdown (KD) of MDM4 provokes growth inhibition across a range of BC subtypes with mutant p53, including luminal, Her..
View full abstractRelated Projects (3)
Grants
Awarded by NHMRC
Awarded by CCV
Awarded by NBCF
Awarded by National Breast Cancer Foundation
Funding Acknowledgements
This work was supported by an NHMRC project grant (1049179) and an NHMRC Fellowship to YH (9628426), by a CCV grant (1085154), and by an innovator grant from NBCF (IN-16-042).