Centrosome amplification can initiate tumorigenesis in flies

被引：442

作者：

Basto, Renata ^{[1
]}

Brunk, Kathrin ^{[1
]}

Vinadogrova, Tatiana ^{[2
,3
]}

Peel, Nina ^{[1
,4
]}

Franz, Anna ^{[1
]}

Khodjakov, Alexey ^{[2
,3
]}

Raff, Jordan W. ^{[1
]}

机构：

[1] Gurdon Inst, Cambridge CB2 1QN, England

[2] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA

[3] SUNY Albany, Dept Biomed Sci, Albany, NY 12222 USA

[4] NIDDK, NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA

来源：

CELL | 2008年 / 133卷 / 06期

基金：

英国惠康基金;

关键词：

D O I：

10.1016/j.cell.2008.05.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1032 / 1042

页数：11

共 63 条

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