SIAH-1 inhibits cell growth by altering the mitotic process

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 proces s. The transfectants show a redistribution of SIAH-1 protein within the nuc leus, more specifically to the nuclear matrix, associated to dramatic chang es in cell morphology and defective mitosis. Multinucleated giant cells (2- 12 nuclei in more than 50% cells) were a most striking observation associat ed with tubulin spindle disorganization and defective cytokinesis, There we re also present at high frequency abortive mitotic figures, DNA bridges and persistance of intercellular bridges and midbodies, along with an increase d expression of p21(Waf-1) These results indicate that the mechanism of gro wth arrest induced by SIAH-1 in MCF-7 cells involves disorganization of the mitotic program, mainly during nuclei separation and cytokinesis.