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Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast

Eddie Myers1, Arnold D K Hill, Gabrielle Kelly

  • 1Department of Surgery, Saint Vincent's University Hospital University College Dublin, Dublin 4, Ireland.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 25, 2005
PubMed
Abstract

Insights

Transcription factors Ets-1 and Ets-2 are linked to poorer breast cancer survival. Their interaction with coactivators SRC-1 and AIB1, and coregulator NCoR, impacts recurrence and HER2 expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • p160 coactivator proteins are implicated in endocrine therapy resistance.
  • Nuclear receptor coregulatory proteins may interact with nonsteroid receptors.

Purpose of the Study:

  • Investigate interactions between mitogen-activated protein kinase-activated transcription factors (Ets) and coactivators SRC-1, AIB1, and corepressor NCoR in human breast cancer.
  • Determine the prognostic significance of these interactions.

Main Methods:

  • Utilized immunohistochemistry and immunofluorescence to assess protein expression and coexpression in 134 breast tumor patients.
  • Employed Western blot, electromobility shift, and coimmunoprecipitation assays to analyze protein expression, DNA interactions, and protein-protein interactions.

Main Results:

  • Ets-1 and Ets-2 expression correlated with reduced disease-free survival (P < 0.0292, P < 0.0001).
  • NCoR served as a positive prognostic indicator (P < 0.0297).
  • Growth factors induced Ets-DNA interactions, coactivator recruitment, and HER2 upregulation, particularly with Ets-2 and SRC-1 coexpression, which strongly associated with recurrence and HER2 expression (P < 0.0001).

Conclusions:

  • Established associations between nonsteroid transcription factors (Ets) and coregulatory proteins in human breast cancer.
  • Demonstrated interactions between Ets proteins, coactivators (SRC-1, AIB1), and corepressor (NCoR).
  • Highlighted the clinical relevance of these interactions in predicting breast cancer prognosis and recurrence.

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