Inhibition of BET bromodomain proteins as a therapeutic approach in prostate cancer.

作者: Anastasia Wyce , Yan Degenhardt , Yuchen Bai , BaoChau Le , Susan Korenchuk

DOI: 10.18632/ONCOTARGET.1572

关键词: BET inhibitorOncogeneBiologyChromatinBromodomainBRD4Cancer researchGene expressionCell growthHistone

摘要: BET (bromodomain and extra-terminal) proteins regulate gene expression through their ability to bind acetylated chromatin subsequently activate RNA PolII-driven transcriptional elongation. Small molecule inhibitors prevent binding of histones inhibit activation target genes. attenuate cell growth survival in several hematologic cancer models, partially the down-regulation critical oncogene, MYC. We hypothesized that will MYC solid tumors frequently over-express Here we describe effects highly specific inhibitor, I-BET762, on prostate models. I-BET762 potently reduced lines a patient-derived tumor model with subsequent inhibition reduction burden vivo. Our data suggests are driven by underlines importance additional mechanisms induced phenotypes.

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