SIAH-1 inhibits cell growth by altering the mitotic process

H. Bruzzoni-Giovanelli, A. Faille, G. Linares-Cruz, M. Nemani, F. Le Deist, A. Germani, D. Chassoux, G. Millot, J. P. Roperch, R. Amson, A. Telerman, F. Calvo

Research output: Contribution to journalArticlepeer-review

Abstract

SIAH-1, the human homologue of the drosophila seven in absentia gene, is a p53-p21(Waf-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 p21(Waf-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.

Original languageEnglish
Pages (from-to)7101-7109
Number of pages9
JournalOncogene
Volume18
Issue number50
Publication statusPublished - Nov 25 1999

Keywords

  • Apoptosis
  • Cytokinesis
  • Mitosis
  • Multinucleated cell
  • p21
  • SIAH-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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