4.8 Article

Centrosome amplification can initiate tumorigenesis in flies

期刊

CELL
卷 133, 期 6, 页码 1032-1042

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CELL PRESS
DOI: 10.1016/j.cell.2008.05.039

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  1. Cancer Research UK Funding Source: Medline
  2. NIGMS NIH HHS [R01 GM059363, R01 GM059363-10] Funding Source: Medline
  3. Wellcome Trust Funding Source: Medline

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Centrosome amplification is a common feature of many cancer cells, and it has been previously proposed that centrosome amplification can drive genetic instability and so tumorigenesis. To test this hypothesis, we generated Drosophila lines that have extra centrosomes in similar to 60% of their somatic cells. Many cells with extra centrosomes initially form multipolar spindles, but these spindles ultimately become bipolar. This requires a delay in mitosis that is mediated by the spindle assembly checkpoint (SAC). As a result of this delay, there is no dramatic increase in genetic instability in flies with extra centrosomes, and these flies maintain a stable diploid genome over many generations. The asymmetric division of the larval neural stem cells, however, is compromised in the presence of extra centrosomes, and larval brain cells with extra centrosomes can generate metastatic tumors when transplanted into the abdomens of wild-type hosts. Thus, centrosome amplification can initiate tumorigenesis in flies.

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