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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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ER regulates an evolutionarily conserved apoptosis pathway.

Zhihua Liu1, Shilin Chen

  • 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China. zhliu@implad.ac.cn

Biochemical and Biophysical Research Communications
|August 10, 2010
PubMed
Summary
This summary is machine-generated.

Estrogen receptor (ER) and FoxA1 binding sites were identified in breast cancer cells. Conserved cis-regulatory elements linked to apoptosis genes were discovered, revealing ER

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Area of Science:

  • Genomics and Molecular Biology
  • Cancer Research
  • Evolutionary Biology

Background:

  • Estrogen receptor (ER) is a key factor in breast cancer development.
  • FoxA1 acts as a pioneer factor, facilitating ER binding to genomic regulatory elements.
  • Standard ChIP-chip methods lack evolutionary conservation context for transcription factor binding sites.

Purpose of the Study:

  • To identify evolutionarily conserved ER and FoxA1 binding sites.
  • To analyze target genes associated with conserved cis-regulatory elements.
  • To investigate the role of conserved elements in regulating apoptosis pathways in breast cancer.

Main Methods:

  • Genome-wide ChIP-chip experiments were performed in MCF-7 cells to map ER and FoxA1 binding sites.
  • The Detection of LinEage-Specific Selection (DLESS) method was employed to identify evolutionarily conserved cis-regulatory elements.
  • Gene expression data and Ingenuity Pathway Analysis (IPA) were used to analyze target genes and construct regulatory networks.

Main Results:

  • A total of 7,877 ER and 18,135 FoxA1 binding sites were identified in MCF-7 cells.
  • The DLESS method identified fully conserved cis-regulatory elements associated with apoptosis-related target genes.
  • Apoptosis genes linked to conserved elements showed significant correlation with ER binding and differential expression in MCF-7 cells.

Conclusions:

  • Estrogen receptor (ER) regulates an evolutionarily conserved apoptosis pathway in breast cancer.
  • Conserved cis-regulatory elements play a crucial role in ER-mediated apoptosis regulation.
  • This study provides new insights into breast cancer apoptosis through the lens of cis-regulatory element evolution.