Centrosome hyperamplification in bladder cancer.

膀胱癌中心体过度扩增。

• 批准号: 13671679
• 负责人: KAWAMURA Kenji
• 金额: $ 1.15万
• 依托单位: KANAZAWA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671679/
• 关键词: Centrosome hyperamplification; p53; Cyclin E; nucleophosmin; Bladder_cancer; 中心体; 過剰複製

1, Centrosome Hyperamplification and Chromosomal Instability in Bladder CancerThe centrosome is composed of a pair of centrioles and surrounding amorphous pericentriolar material. The centrosome duplication cycle is a highly regulated process, and abrogation of the regulatory mechanism results in uncontrolled amplification of centrosomes. Centrosome hyperamplification (CH) leads to formation of multipolar spindles and unequal segregation of chromosomes to daughter cells. The variability in chromosome number observed in tumor cells has recently been termed chromosomal instability (CIN). There are many potential causes for this chromosomal instability. Centrosome hyperamplification (CH) occurs frequently in human cancers, and may be a major contributing factor to CIN. We investigated CH in bladder cancer, and estimated the relationship between CH and CIN. The centrosome replication cycle is well regulated in a pathologically low grade bladder cancer cell line (RT-4) which does not have c … More hromosomal instability. In contrast, we found a dramatic variability of centrosomes in pathologically high grade bladder cancer cell lines (HT-1197 and HT-1376) which have chromosomal instability. CH and CIN occur together in invasive bladder cancer cell lines. CH may be the major contributing factor for CIN and may be involved in tumor development and progression in bladder cancer.2, Centrosome Isolation from Cultured Bladder Cancer Cells.We used sucrose gradient fractions enriched for centrosomes by the immunoblot analysis for the presence of γ-tubulin, a major component of centrosomes. The fractions were then immunoblotted with anti-nucleophosmin/B23 (NPM) antibody. NPM is a primary target of CDK2-cyclin E in the initiation of centrosome duplication. The profile of NPM closely paralleled that of γ-tubulin, suggesting the association of NPM with the centrosome. Identification of the mechanism underlying the replication of the centrosome should lead to the understanding of the mechanism of chromosomal instability in bladder cancer, and enable us to develop cancer therapeutics targeted to centrosome replication. Less

膀胱癌中心体过度扩增与染色体不稳定中心体由一对中心粒和周围无定形的中心粒周围物质组成。中心体复制周期是一个高度调控的过程，而调控机制的废除会导致中心体的不受控制的扩增。中心体超扩增（CH）导致多极纺锤体的形成和染色体向子细胞的不均等分离。在肿瘤细胞中观察到的染色体数目的变异性最近被称为染色体不稳定性（CIN）。这种染色体不稳定性有许多潜在的原因。中心体过度扩增（CH）在人类癌症中频繁发生，并且可能是CIN的主要促成因素。我们研究了膀胱癌中CH的表达，并探讨了CH与CIN的关系。中心体复制周期在病理学低级别膀胱癌细胞系（RT-4）中得到很好的调节，该细胞系不具有C ...更多信息 染色体不稳定性与此相反，我们发现了一个显着的变化，中心体在病理高级别的膀胱癌细胞系（HT-1197和HT-1376），具有染色体不稳定性。CH和CIN在浸润性膀胱癌细胞系中一起发生。CH可能是CIN的主要促成因素，并且可能参与膀胱癌的肿瘤发展和进展。2，从培养的膀胱癌细胞中分离中心体。我们使用通过免疫印迹分析γ-微管蛋白（中心体的主要组分）的存在而富集中心体的蔗糖梯度组分。然后用抗核磷蛋白/B23（NPM）抗体对级分进行免疫印迹。NPM是CDK 2-cyclin E启动中心体复制的主要靶点。NPM与γ-tubulin的图谱非常接近，提示NPM与中心体有关。中心体复制机制的确定将有助于我们理解膀胱癌中染色体不稳定的机制，并使我们能够开发针对中心体复制的癌症治疗方法。少

项目成果

Kenji Kawamura, et al.: "Centrosome hyperamplification and chromosomal instability in bladder cancer"European Urology. (in press). (2003)

Kenji Kawamura 等人：“膀胱癌中的中心体过度扩增和染色体不稳定”欧洲泌尿学。

Kenji Kawamura, et al.: "Centrosome Hyperamplification and Chromosomal Instability in Bladder Cancer"J. Kanazawa Med.. 27. 237-242 (2003)

Kenji Kawamura 等人：“膀胱癌中的中心体过度扩增和染色体不稳定性”J。

川村研二, 他: "膀胱癌における中心体過剰複製と染色体不安定性について"金沢医科大学雑誌. 27. 237-242 (2003)

Kenji Kawamura 等人：“膀胱癌中的中心体过度复制和染色体不稳定”金泽医科大学杂志 27. 237-242 (2003)。

川村研二, 他: "膀胱癌細胞株からの中心体分離-p53 mutationと中心体過剰複製について-"泌尿器紀要. 49. 69-74 (2003)

Kenji Kawamura 等人：“从膀胱癌细胞系中分离中心体 - p53 突变和中心体过度复制 -”《泌尿学通报》49. 69-74 (2003)。

川村研二・他: "膀胱癌における中心体過剰複製と染色体不安定性について"金沢医科大学雑誌. (in press). (2003)

Kenji Kawamura 等人：“膀胱癌中的中心体过度复制和染色体不稳定”金泽医科大学杂志（2003 年）。