Activation of rapid oestrogen signalling in aggressive human breast cancers

Authors

  • Coralie Poulard,

    1. Université de Lyon, Lyon, France
    2. Université Lyon 1, Lyon, France
    3. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    4. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    5. Centre Léon Bérard, Lyon, France
    6. Equipe Labellisée, La Ligue, France
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Isabelle Treilleux,

    1. Université de Lyon, Lyon, France
    2. Université Lyon 1, Lyon, France
    3. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    4. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    5. Centre Léon Bérard, Lyon, France
    6. Equipe Labellisée, La Ligue, France
    7. Pathology Department, Centre Léon Bérard, Lyon, France
    Search for more papers by this author
    • These authors contributed equally to this work.

  • Emilie Lavergne,

    1. Biostatistics Unit, Centre Léon Bérard, Lyon, France
    Search for more papers by this author
  • Katia Bouchekioua-Bouzaghou,

    1. Université de Lyon, Lyon, France
    2. Université Lyon 1, Lyon, France
    3. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    4. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    5. Centre Léon Bérard, Lyon, France
    6. Equipe Labellisée, La Ligue, France
    Search for more papers by this author
  • Sophie Goddard-Léon,

    1. Pathology Department, Centre Léon Bérard, Lyon, France
    Search for more papers by this author
  • Sylvie Chabaud,

    1. Biostatistics Unit, Centre Léon Bérard, Lyon, France
    Search for more papers by this author
  • Olivier Trédan,

    1. Department of Medical Oncology, Centre Léon Bérard, Lyon, France
    Search for more papers by this author
  • Laura Corbo,

    1. Université de Lyon, Lyon, France
    2. Université Lyon 1, Lyon, France
    3. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    4. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    5. Centre Léon Bérard, Lyon, France
    6. Equipe Labellisée, La Ligue, France
    Search for more papers by this author
  • Muriel Le Romancer

    Corresponding author
    1. Université de Lyon, Lyon, France
    2. Université Lyon 1, Lyon, France
    3. Inserm U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    4. CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Lyon, France
    5. Centre Léon Bérard, Lyon, France
    6. Equipe Labellisée, La Ligue, France
    • Tel: +33 4 78 78 28 22; Fax: +33 4 78 78 27 20

    Search for more papers by this author

Abstract

Oestrogen receptors can mediate rapid activation of cytoplasmic signalling cascades by recruiting Src and PI3K. However, the involvement of this pathway in breast cancer remains poorly defined. We have previously shown that methylation of ERα is required for the formation of the ERα/Src/PI3K complex and that ERα is hypermethylated in a subset of breast cancers. Here, we used Proximity Ligation Assay to demonstrate that this complex is present in the cytoplasm of breast cancer cell lines as well as formalin-fixed, paraffin-embedded tumours. Of particular interest, the analysis of 175 breast tumours showed that overexpression of this complex in a subset of breast tumours correlates to the activation of the downstream effector Akt. Survival analysis revealed that high expression of this complex is an independent marker of poor prognosis and associated with reduced disease-free survival. Our data introduces the new concept that the rapid oestrogen pathway is operative in vivo. It also provides a rationale for patient stratification defined by the activation of this pathway and the identification of target therapies.

Ancillary