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Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells.

ABSTRACT: Aberrations in centrosome numbers have long been implicated in aneuploidy and tumorigenesis, but their origins are unknown. Here we have examined how overexpression of Aurora-A kinase causes centrosome amplification in cultured cells. We show that excess Aurora-A does not deregulate centrosome duplication but gives rise to extra centrosomes through defects in cell division and consequent tetraploidization. Over expression of other mitotic kinases (Polo-like kinase 1 and Aurora-B) also causes multinucleation and concomitant increases in centrosome numbers. Absence of a p53 checkpoint exacerbates this phenotype, providing a plausible explanation for the centrosome amplification typical of p53-/- cells. We propose that errors during cell division, combined with the inability to detect the resulting hyperploidy, constitute a major cause for numerical centrosome aberrations in tumors.

SUBMITTER: Meraldi P

PROVIDER: S-EPMC125866 | biostudies-literature | 2002 Feb

REPOSITORIES: biostudies-literature

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Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells.

Meraldi Patrick P Honda Reiko R Nigg Erich A EA

The EMBO journal 20020201 4

Aberrations in centrosome numbers have long been implicated in aneuploidy and tumorigenesis, but their origins are unknown. Here we have examined how overexpression of Aurora-A kinase causes centrosome amplification in cultured cells. We show that excess Aurora-A does not deregulate centrosome duplication but gives rise to extra centrosomes through defects in cell division and consequent tetraploidization. Over expression of other mitotic kinases (Polo-like kinase 1 and Aurora-B) also causes mul ...[more]

PMID: 11847097

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