Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression
Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression
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DOI：
10.1038/sj.onc.1202515
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发表时间：
1999-03-18
期刊：
影响因子：
8
通讯作者：
Fukasawa, K
中科院分区：
文献类型：
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作者：
Carroll, PE;Okuda, M;Fukasawa, K
我们以前曾报道过p53肿瘤抑制蛋白的缺失导致中心体过度扩增，这导致异常的有丝分裂和染色体不稳定。由于p53在人类癌症中以高频率缺失或突变，我们研究了人类癌症是否表现出中心体过度扩增，对晚期乳腺导管癌和头颈部鳞状细胞癌（SCCHN）的筛查显示，中心体过度扩增在两种肿瘤类型中都很常见，此外，通过直接测序和杂合性丢失试验分析SCCHN样本中的p53，我们发现p53突变与中心体超扩增的发生相关。然而，在某些情况下，我在保留野生型p53的肿瘤中观察到中心体过度扩增，这些肿瘤含有高水平的Mdm2，由于Mdm2可以通过物理结合使p53失活，我们研究了Mdm2过表达是否诱导中心体过度扩增，我们发现Mdm2过表达，就像p53的丢失一样，诱导培养细胞中中心体过度扩增和染色体不稳定。
We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperamplification, which leads to aberrant mitosis and chromosome instability, Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperamplification, Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperamplification is frequent in both tumor types, Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperamplification. However, in some cases, me observed centrosome hyperamplification in tumors that retained wild-type p53, These tumors contained high levels of Mdm2, Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperamplification, We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperamplification and chromosome instability in cultured cells.