The study of Abnormal Amplification of Centrosome in bladder cancer
| Project/Area Number |
15591720
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | KANAZAWA MEDICAL UNIVERSITY |
|---|
Principal Investigator |
SHIBA Nobuyuki (2004) Kanazawa Medical University, Urology, Assistant professor, 医学部, 講師 (30247457)
池田 龍介 (2003) 金沢医科大学, 医学部, 助教授 (90151307)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KAWAMURA Kenji Kanazawa Medical University, Urology, Assistant professor, 医学部, 講師 (40224852)
TANAKA Tatsuro Kanazawa Medical University, Urology, Assistant professor, 医学部, 講師 (70188308)
芝 延行 金沢医科大学, 医学部, 講師 (30247457)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
|
|---|
| Keywords | centrosome amplification / chromosome instability / cyclin E / p53 / 中心体 / 放射線照射 / G2停止 / 膀胱癌 / P53 |
|---|
| Research Abstract |
The centrosome, which is composed of a pair of centrioles and surrounding amorphous pericentriolar material, is a major microtubule organizing center in animal cells. Its most prominent function is observed during mitosis, in which the duplicated centrosomes form the spindle poles, which direct spindle microtubule assembly and establish bipolarity, both of which are required for accurate segregation of chromosomes into daughter cells.
Centrosome amplification frequently occurs in human cancers and is a major cause of chromosome instability (CIN). In mouse cells, centrosome amplification can be readily induced by loss or mutational inactivation of p53. In human cells, however, silencing of endogenous p53 alone does not induce centrosome amplification or CIN, although high degrees of correlation between p53 mutation and CIN/centrosome amplification in human cancer can be detected, suggesting the presence of additional regulatory mechanism(s) in human cells that ensures the numeral integri
… More
ty of centrosomes and genomic integrity. Cyclin E, a regulatory subunit for CDK2 that plays a key role in centrosome duplication, frequently is overexpressed in human cancers. We found that cyclin E overexpression, together with loss of p53, efficiently induces centrosome amplification and CIN in human bladder cancer cells but not by either cyclin E overexpression or loss ofp53 alone. We extended these findings to bladder cancer specimens and found that centrosome amplification is strongly correlated with concomitant occurrence of cyclin E overexpression and p53 inactivation but not with either cyclin E overexpression or p53 inactivation alone. Because cyclin E expression is strictly controlled in human cells compared with mouse cells, our findings suggest that this stringent regulation of cyclin E expression plays an additional role underlying numeral homeostasis of centrosomes in human cells and that deregulation of cyclin E expression, together with inactivation of p53, results in centrosome amplification. Less
|
Report
(3 results)
Research Products
(5 results)
