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  • Original Paper
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SIAH-1 inhibits cell growth by altering the mitotic process

Oncogene volume 18, pages 7101–7109 (1999)Cite this article

Abstract

SIAH-1, the human homologue of the drosophila seven in absentia gene, is a p53-p21Waf-1 inducible gene. We report that stable transfection with SIAH-1 of the epithelial breast cancer cell line MCF-7 blocks its growth process. The transfectants show a redistribution of SIAH-1 protein within the nucleus, more specifically to the nuclear matrix, associated to dramatic changes in cell morphology and defective mitosis. Multinucleated giant cells (2 – 12 nuclei in more than 50% cells) were a most striking observation associated with tubulin spindle disorganization and defective cytokinesis. There were also present at high frequency abortive mitotic figures, DNA bridges and persistance of intercellular bridges and midbodies, along with an increased expression of p21Waf-1. These results indicate that the mechanism of growth arrest induced by SIAH-1 in MCF-7 cells involves disorganization of the mitotic program, mainly during nuclei separation and cytokinesis.

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Acknowledgements

We wish to thank Dr S Gisselbrecht for helpful discussions. H Bruzzoni-Giovanelli is recipient of a grant from the French Government and was recipient of a grant from Conicyt Uruguay. This work was supported by grants from ECOS program and Association pour la Recherche Contre le Cancer (ARC) France to F Calvo.

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Authors and Affiliations

  1. Laboratoire de Pharmacologie Expérimentale et Clinique INSERM EP-9932. Institut de Génétique Moléculaire. Hópital Saint-Louis., 27 rue Juliette Dodu, Paris, 75010, France

    H Bruzzoni-Giovanelli, A Faille, G Linares-Cruz, G Millot & F Calvo

  2. Fondation Jean-Dausset - CEPH, Paris, France

    M Nemani, J-P Roperch, R Amson & A Telerman

  3. INSERM Unité 429 Hópital Necker, Paris, France

    F Le Deist

  4. INSERM Unité 363 Hópital Cochin, Paris, France

    A Germani

  5. INRA Unité 806 Institut Curie, Paris, France

    D Chassoux

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  1. H Bruzzoni-Giovanelli
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Bruzzoni-Giovanelli, H., Faille, A., Linares-Cruz, G. et al. SIAH-1 inhibits cell growth by altering the mitotic process. Oncogene 18, 7101–7109 (1999). https://doi.org/10.1038/sj.onc.1203187

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  • DOI: https://doi.org/10.1038/sj.onc.1203187

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