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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Gene expression profiling of ErbB receptor and ligand-dependent transcription

Dhara N Amin1, Archibald S Perkins, David F Stern

  • 1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06510, USA.

Oncogene
|February 20, 2004
PubMed

Insights

ErbB2 and ErbB4 receptors in breast cancer have different effects on gene expression. Understanding these distinct pathways, including novel targets like EPS15R and HRY/HES1, is crucial for targeted therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • ErbB2 and ErbB4 receptor overexpression in breast cancer correlates with varied clinical outcomes.
  • The molecular mechanisms underlying these differential outcomes require elucidation.

Purpose of the Study:

  • To comparatively investigate gene expression regulated by ErbB2 and ErbB4 receptors.
  • To identify distinct transcriptional targets of isolated ErbB2 and ErbB4 activation in breast cancer cells.

Main Methods:

  • Utilized agonistic antibodies to selectively activate ErbB2 and ErbB4 in breast cancer cell lines.
  • Performed gene expression profiling using a 16,755-gene oligonucleotide array to identify transcriptional targets.

Main Results:

  • ErbB2 and ErbB4 activation differentially influence gene transcription within the same cell line.
  • Identified both shared and receptor-specific transcriptional targets for ErbB2 and ErbB4.
  • Discovered novel ErbB signaling targets, including EPS15R, GATA4, RAB2 (ErbB4) and HRY/HES1, PPAP2A (ErbB2).

Conclusions:

  • ErbB2 and ErbB4 signaling pathways exhibit distinct gene regulatory profiles.
  • Specific ErbB2 homodimer targets may serve as valuable biomarkers in breast cancer, particularly given common overexpression and ligand-independent activation.

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