| Project/Area Number |
11557136
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
YONEDA Toshiyuki Osaka University Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (80142313)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIMURA Riko Osaka University Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (60294112)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,500,000 (Direct Cost: ¥13,500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥11,100,000 (Direct Cost: ¥11,100,000)
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| Keywords | Cancer / Bone metastases / TGF-beta / Soft tissues metastases / Bone resorption / Smad / DDR1 / Bisphosohonate / TGF-β / IGF-1 / TGF / 遠隔転移 / 乳癌 / 前立腺癌 / レポーターアッセイ |
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| Research Abstract |
(1) Role of TGF-beta and IGF-1 in bone metastases of breast cancers
In bone tissues/there are large amount of Transforming growth factor-beta (TGF-beta) and Insulin-like growth factor-1 (IGF-1), it is, therefore, likely that these two major growth factors play some roles in bone remodeling in physiological or pathological conditions. It is well know that breast cancers resorb the bone after metastasizing into bone. To examine the role of IGF-1 in bone metastases, we established the breast cancer cell line MDA231 overexpressing dominant-negative IGF-1 receptor, and assessed its bone-metastatic effects using animal model. We found that the cell line showed much less bone metastatic activity compared with parental MDA231 cells. We next evaluated the effects of TGF-beta on MDA231 cells. TGF-beta had little effects on the growth of MDA231 cells but markedly enhanced the production of PTHrP which is one of the important factor in bone metastases by cancers. In addtion, TGF-beta activates the Smad signaling through Smad2, Smad3 and Smad4. Finally, we found the breast cancer cell line that is deficient in Smad4 showed no ability to metastasize into bone. These finding suggest that important roles of TGF-beta and IGF-1 in bone metastases by breast cancers.
(2) The effects of bisphosphonate on soft-tissue metastases of breast cancers
It is well know that bisphosphonate is a powerful inhibitor for osteoclasts and useful to treat the bone metastasized cancers. However, little is know the effects on soft tissue metastases of breast cancers. To address this, we established the system in which we can evaluate the bone metastases as well as soft tissues metastases. Using this system, we found that bisphosphonate blocked the bone metastases but stimulated the metastases into soft tissues such as lung and liver. It is likely that bisphosphonate has distinct effects on bone and soft tissues.
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