| Project/Area Number |
09470138
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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 | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
KAWATA Sumio Osaka University Medical School, Associate Professor, 医学部, 助教授 (90183285)
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| Co-Investigator(Kenkyū-buntansha) |
KISO Shinichi Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
FUKUDA Kazuto Osaka University Hospital, Medical Staff, 医学部・附属病院, 医員
TAMURA Shinji Osaka University Medical School, Assistant Professor, 医学部, 助手 (30243223)
松田 幸彦 大阪大学, 医学部, 助手 (90283770)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1998: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Keywords | Hepatocellular carcinoma / TGF-b / TGF-b receptor / gene mutation / cell growth |
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| Research Abstract |
We are studying on altered control on hepatocytes growth during the carcinogensis. The altered regulation seems to be derived from escape from negative growth control by TGF-b via , a loss of responsivity of hepatocytes. Our hypothesis is that ther is not only defect of TGF-b receptor but also alteration of the signal transduction pathway of the cytokine.
To determined wether Src kinase is involved in TGF-b signaling, we examined the effects of TGF-b1 on Src in rat fibroblast- cell line 3Y1 and in v-Src-transformed 3Y1 (SR-3Y1). TGF-b1 inhibited MAP kinase activity and inhibited growth in SR-3Y1 cells, while it did not affect the growth of 3Y1 cells. TGF-b1 significantly decreased v-Src kinase activity and protein abundance in SR-3Y1 cells, mainly by accelerating the degradation of v-Src. In contrast, in 3Y1 cells, TGF-b1 did not affect c-Src abandance or kinase activity. however, upon activation of c-Src in 3Y1 cells by PDGF, TGF-b1 decreased Src abundance. Additionally, in 3Y1 cells transfected with an activated c-Src mutant which lacks the SH3 domain, its level was decreased by TGF-b1 treatment. These findings suggest that TGf-b1 specifically induces degradation of activated Src kinase. This may be a novel mechanism for cross-talk between growth factors and TGF-b.
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