Related Experiment Video

Updated: Aug 18, 2025

Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Bromodomain Protein BRD4-Mediated Mutant p53 Transcription Promotes TNBC Progression

Julie Xia Zhou1,2, Ewud Agborbesong1,2, Linda Xiaoyan Li1,2

  • 1Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA .

International Journal of Molecular Sciences
|December 11, 2022
PubMed

Insights

Bromodomain protein BRD4 upregulates mutant p53 in triple-negative breast cancer (TNBC). Inhibiting BRD4 suppresses mutant p53, reducing TNBC cell growth and tumor formation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • TP53 mutations are common in human cancers, leading to oncogenic mutant p53.
  • Mutant p53 is a therapeutic target, but its epigenetic regulation is poorly understood.
  • Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options.

Purpose of the Study:

  • To investigate the epigenetic regulation of mutant p53 in TNBC.
  • To identify novel therapeutic targets for TNBC by understanding mutant p53 regulation.

Main Methods:

  • Utilized TNBC cell lines and in vivo xenograft models.
  • Employed BRD4 inhibition using the small molecule inhibitor JQ1.
  • Performed gene knockdown experiments targeting BRD4.
  • Assessed p53 and p21 expression levels, cell cycle progression, and colony formation.

Main Results:

  • BRD4 was identified as a key mediator of mutant p53 upregulation in TNBC cells.
  • BRD4 inhibition (JQ1 or knockdown) suppressed mutant p53 transcription, leading to p21 re-expression and reduced proliferation.
  • BRD4 also regulated wild-type p53, affecting p21 expression in non-TNBC cells (MCF-7).
  • BRD4 knockdown significantly attenuated TNBC tumor growth in vivo.

Conclusions:

  • BRD4 plays a critical role in the epigenetic regulation of mutant p53 in TNBC.
  • Targeting BRD4 with inhibitors like JQ1 offers a potential therapeutic strategy for TNBC by suppressing mutant p53.
  • This study uncovers a novel mechanism for controlling mutant p53 and inhibiting tumorigenesis in TNBC.
Keywords:
BRD4p53triple-negative breast cancer

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