| Project/Area Number |
21790311
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
TAKENAKA Katsuya Tokyo Medical and Dental University, 難治疾患研究所, 助教 (20378706)
|
|---|
| Project Period (FY) |
2009 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| Keywords | 分子腫瘍学 / BRCA2 / 乳癌 / DNA損傷修復 / nucleophonsmin / ROCK2 / DR-GFP / U2OS / 質量分析 |
|---|
| Research Abstract |
BRCA2 germline mutations account for the majority of heredity breast and ovarian cancer. Besides its role in DNA damage repair, it was hypothesized that BRCA2 might have a role in centrosomal amplification, since BRCA2 localizes to centrosomes as well as nuclei and the dysfunction of BRCA2 in a centrosome causes abnormalities in cell division. We identified nucleophosmin (NPM) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) as novel BRCA2-associated proteins by mass spectrometry. Because it is known that ROCK2 binds to NPM at centrosomes, these 3 proteins may form a complex. NPM-binding region in BRCA2 was determined to be within amino acids 639-1,000. Exogenous expression of this BRCA2 region resulted in aberrant centrosome amplification and a high frequency of multinucleated cells. Our results suggested that a complex consisting of BRCA2, NPM, and ROCK2 maintains the numerical integrity of centrosomes and accurate cell division and that dysfunction of this regulation might be involved in the tumorigenesis of breast cancer.
|
