| Project/Area Number |
09670484
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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 |
内科学一般
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| Research Institution | Sapporo Medical University School of Medicine |
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Principal Investigator |
ADACHI Masaaki Sapporo Medical University, Sch. Of Med., First Dept. Of Internal Medicine, Associated Professor, 医学部, 助教授 (70240926)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Kohzoh Sapporo Medical University, School of Medicine, First Department of Internal Medicine, Professor, 医学部, 教授 (60117603)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | Bcl-2 / BAG-1 / Metastasis / anoikis / Golgi apparatus / Cell motility / BAD / 細胞運動能 |
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| Research Abstract |
Apoptosis is tightly linked to cellular differentiation and development. In addition to these physiological functions, we found that suppression of apoptosis promotes cancer metastasis and dissemination. In this regard, anti-apoptotic molecules are considered to be oncogenic proteins, and our data strongly suggest that suppression of anti-apoptotic molecules may inhibit tumor progression, especially metastasis and dissemination. In this project, we have investigated whether overexpression of dominant negative form of Bcl-2/BAG-1 can lead to decrease of tumor progression. So far, we could not obtain conclusive results on this issue. However, we also explored several points regarding BAG-1 functions and demonstrated that BAG-1 can contribute to cell motility through interaction with cytokeratin and actin filaments. We also found that BAG-1 accumulates at the Golgi apparatus in normal epithelial cells. Importantly, the intracellular localization of BAG-1 is disrupted in carcinoma cells. The aberrant distribution of BAG-1 in carcinoma cells may be associated with malfunction of BAG-1 and alter cellular properties and contribute to cancer development. In addition, we found that activation of PKC alpha increases sensitivity to anoikis, and thus the activation may be useful for inhibition of metastasis, since cancer cells can not attach extracellular matrix during metastasis.
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