| Project/Area Number |
17590257
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
IZUMI Hiroto University of Occupational and Environmental Health, Japan, School of Medicine, Associate professor (50289576)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,410,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Cold shock protein / dbpA / dbpB / dbpC / YB-1 / Contrin / Transcription factor / Gene expression / contrin |
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| Research Abstract |
The result of this study is next (1)〜(7). (1)We analyzed molecular mechanism of the paclitaxel resistance in the breast cancer., As a result, it was thought that dbpB/YB-1 was the important molecule which participated in paclitaxel resistance in the breast cancer. (2) We made an antibody against dbpC/Contrin and examined the expression of normal and cancer tissue. As a result, it was suggested that dbpC/Contrin became a Cancer/Testis Antigen. (3) We examined the gene expression of dbpC/Contrin in the germ cell tumor and the localization in the cell. As a result, we identified an important lesion in the promoter and an important domain that controlled cellular localization in a C terminus of dbpC/Contrin. (4) YB-1 knock-out mice was embryonic lethal and exhibited exencephaly associated with reduction of β-Actin expression and F-actin formation. In addition, fibroblasts derived from YB-1 (-/-) embryos demonstrated reduced growth and cell density. These results demonstrated that YB-1 was involved in early mouse development. (5) We investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. It was suggested that Akt activation regulated the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. (6) We found that Twist was overexpressed in cisplatin-resistant cells, and it was suggested that YB-1 was a target gene of Twist and that YB-1 and Twist expression could induce tumor cell growth. (7) We found that Twist was associated with tumor suppressor gene product p53, and these interaction reduced p21 gene expression activated by p53 and YB-1 gene expression activated by Twist. Furthermore we clarified molecular mechanism of these transcriptional repressions.
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