Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells

Teemu T Junttila1, Maria Sundvall, Mikael Lundin

  • 1Medicity Research Laboratory, Departments of Medical Biochemistry and Molecular Biology, and Turku Postgraduate School of Biomedical Sciences, University of Turku, Finland.

Cancer Research
|March 1, 2005
PubMed

Insights

The ErbB4 receptor

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ErbB1 and ErbB2 receptors are established anticancer targets.
  • The clinical role of the ErbB4 receptor in breast cancer remains unclear.

Purpose of the Study:

  • To investigate the clinical significance of proteolytically cleavable ErbB4 isoforms in breast cancer.
  • To explore the in vitro functions of ErbB4 in breast cancer cells.

Main Methods:

  • Real-time reverse transcription-PCR analysis of 62 breast cancer samples.
  • Immunohistochemistry on 458 breast cancer patients.
  • In vitro overexpression studies in ER-positive breast cancer cells.

Main Results:

  • Cleavable ErbB4 isoforms correlate with estrogen receptor-alpha (ER) expression and high histologic grade.
  • High ErbB4 protein expression is linked to favorable outcomes in ER-positive breast cancer.
  • Nuclear ErbB4 immunoreactivity is associated with poor survival, unlike membranous staining.
  • In vitro, ErbB4 promoted proliferation and transcriptional activity in ER-positive cells.

Conclusions:

  • ErbB4's clinical impact in breast cancer depends on its subcellular localization.
  • A cleavable ErbB4 isoform promotes ER-positive breast cancer growth and enhances ER-mediated transcription.

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