Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability

被引:135
作者
Castellanos, Elisabeth [1 ]
Dominguez, Paloma [1 ]
Gonzalez, Cayetano [1 ,2 ]
机构
[1] IRB Barcelona, Cell Div Grp, PCB, Barcelona 08028, Spain
[2] Passeig Lluis Co 23, Inst Catalana Recerca & Estudis Avancats, Barcelona 08010, Spain
关键词
D O I
10.1016/j.cub.2008.07.029
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
Genome instability (GI) and centrosomal alterations are common traits in human cancer [1, 2]. it is suspected that centrosome dysfunction may cause tumors by bringing about GI, but direct experimental proof is still lacking [3]. To explore the possible functional link between centrosome function and overgrowth, we have assayed the tumorigenic potential of a series of mutants that affect different centrosomal proteins in Drosophila. We have found that a significant number of such mutant conditions are tumorigenic in larval brain tissue, where self-renewing asymmetric division of neural stem cells is frequent, but not in symmetrically dividing epithelial cells. We have also found that mutations that increase GI without causing centrosome dysfunction are not tumorigenic in our assay. From these observations, we conclude that the tumors caused by centrosome dysfunction cannot be explained solely by the resulting genome instability. We propose that such tumors might be caused by impaired asymmetric division of neural stem cells [4]. These results show that centrosome loss, far from being innocuous, is a potentially dangerous condition in flies.
引用
收藏
页码:1209 / 1214
页数:6
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