| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
1, Centrosome Hyperamplification and Chromosomal Instability in Bladder Cancer
The 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
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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
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