nsc-146109 and Triple-Negative-Breast-Neoplasms

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, Her2

Topics: Anthracenes; Carcinogenesis; Cell Cycle Proteins; Cell Line; Cell Proliferation; Female; Gene Knockdown Techniques; Humans; Mutation; Nuclear Proteins; Proto-Oncogene Proteins; Thiourea; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53