Castellanos Elisabeth, Dominguez Paloma, Gonzalez Cayetano
Cell Division Group, IRB-Barcelona, PCB, c/ Baldiri Reixac 10-12, 08028 Barcelona, Spain.
Curr Biol. 2008 Aug 26;18(16):1209-14. doi: 10.1016/j.cub.2008.07.029. Epub 2008 Jul 24.
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.
基因组不稳定(GI)和中心体改变是人类癌症的常见特征[1,2]。有人怀疑中心体功能障碍可能通过导致基因组不稳定而引发肿瘤,但仍缺乏直接的实验证据[3]。为了探索中心体功能与过度生长之间可能的功能联系,我们检测了一系列影响果蝇不同中心体蛋白的突变体的致瘤潜力。我们发现,大量此类突变情况在幼虫脑组织中具有致瘤性,在那里神经干细胞频繁进行自我更新的不对称分裂,但在对称分裂的上皮细胞中则不然。我们还发现,在我们的检测中,增加基因组不稳定但不引起中心体功能障碍的突变并不具有致瘤性。从这些观察结果中,我们得出结论,由中心体功能障碍引起的肿瘤不能仅仅用由此产生的基因组不稳定来解释。我们提出,此类肿瘤可能是由神经干细胞不对称分裂受损所致[4]。这些结果表明,中心体缺失在果蝇中绝非无害,而是一种潜在的危险状况。