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Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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Negative Regulator Molecules

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Related Experiment Video

Updated: Jun 16, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

BRCA1 represses amphiregulin gene expression.

Ekaterina P Lamber1, Andrew A Horwitz, Jeffrey D Parvin

  • 1Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts, USA.

Cancer Research
|January 28, 2010
PubMed
Summary

BRCA1 loss of function increases amphiregulin (AREG) protein levels by upregulating its transcription. This study identifies direct BRCA1 regulation of AREG, a key finding in breast cancer development.

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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
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Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

Related Experiment Videos

Last Updated: Jun 16, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1
08:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • BRCA1 is a tumor suppressor gene critical for preventing breast and ovarian cancers.
  • BRCA1's function can be context-dependent, acting as either a transcriptional repressor or activator.
  • Dysregulation of BRCA1 is implicated in various cancer pathologies.

Purpose of the Study:

  • To identify genes transcriptionally regulated by BRCA1.
  • To elucidate the mechanism of BRCA1-mediated transcriptional repression, specifically focusing on amphiregulin (AREG).
  • To establish a link between BRCA1 dysfunction and AREG upregulation in breast cancer.

Main Methods:

  • Microarray analysis of cells with depleted BRCA1 to identify regulated genes.
  • Chromatin immunoprecipitation (ChIP) assays to detect BRCA1 binding to target gene promoters.
  • Identification and mapping of BRCA1 response elements (BRREs) on the AREG promoter.

Main Results:

  • BRCA1 depletion led to the upregulation of specific genes, including amphiregulin (AREG) and early growth response-1 (EGR1).
  • BRCA1 directly binds to the AREG promoter, indicating direct transcriptional repression.
  • Two distinct BRCA1 response elements were identified on the AREG promoter, crucial for BRCA1-mediated repression.
  • BRCA1 depletion resulted in increased AREG protein levels.

Conclusions:

  • Loss of BRCA1 function leads to the upregulation of AREG transcription and protein.
  • BRCA1 directly represses AREG gene expression through specific promoter elements.
  • The identified BRCA1-AREG regulatory pathway is frequently altered in breast cancer, highlighting its potential role in tumorigenesis.