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Short Communication| Volume 45, ISSUE 3, P321-327, February 2009

The oncogenic activity of the Src family kinase Hck requires the cooperative action of the plasma membrane- and lysosome-associated isoforms

  • Renaud Poincloux
    Affiliations
    CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne, F-31077 Toulouse, France

    Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France
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  • Talal Al Saati
    Affiliations
    Plateau Technique d’histopathologie expérimentale, Inserm-IFR30/Génopole Toulouse-Midi Pyrénées, Toulouse, France
    Search for articles by this author
  • Author Footnotes
    d These authors are co-last authors and co-corresponding authors.
    Isabelle Maridonneau-Parini
    Correspondence
    Corresponding authors: Isabelle Maridonneau-Parini, Université Paul Sabatier, Institut de Pharmacologie et de Biologie structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France. Tel.: +33 561 17 54 58; fax: +33 561 17 59 94 (V. Le Cabec); tel.: +33 561 17 54 54 (I. Maridonneau-Parini).
    Footnotes
    d These authors are co-last authors and co-corresponding authors.
    Affiliations
    CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne, F-31077 Toulouse, France

    Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France
    Search for articles by this author
  • Author Footnotes
    d These authors are co-last authors and co-corresponding authors.
    Véronique Le Cabec
    Correspondence
    Corresponding authors: Isabelle Maridonneau-Parini, Université Paul Sabatier, Institut de Pharmacologie et de Biologie structurale, CNRS UMR 5089, 205 route de Narbonne, 31077 Toulouse, France. Tel.: +33 561 17 54 58; fax: +33 561 17 59 94 (V. Le Cabec); tel.: +33 561 17 54 54 (I. Maridonneau-Parini).
    Footnotes
    d These authors are co-last authors and co-corresponding authors.
    Affiliations
    CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), 205 Route de Narbonne, F-31077 Toulouse, France

    Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France
    Search for articles by this author
  • Author Footnotes
    d These authors are co-last authors and co-corresponding authors.
Published:December 29, 2008DOI:https://doi.org/10.1016/j.ejca.2008.11.020

      Abstract

      Hck is a phagocyte specific proto-oncogene of the Src family expressed as two isoforms, p59Hck and p61Hck. It plays a critical role in Bcr/Abl-chronic myeloid leukaemia and is able to transform fibroblasts in vitro. However, the tumourigenic activity of Hck and the respective oncogenic functions of Hck isoforms have not been examined. Tet-Off fibroblasts expressing constitutively active mutants of p59Hck and p61Hck together or individually were used. In contrast to cells expressing p59Hckca or p61Hckca alone, cells expressing both isoforms were transformed in vitro and induced tumour formation in 90% of nude mice within 2 weeks. This is the first demonstration of (i) the tumourigenic activity of Hck in mice, (ii) the cooperative action of the two Hck isoforms in vitro and in vivo. To our knowledge, this is the first example of a transforming activity ‘split’ in two requisite isoforms.

      Keywords

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