1998 Fiscal Year Final Research Report Summary
ALTERED GROWTH CONTROL OF HEPATOCYTES DURING THE CARCINOGENESIS AND ITS REGULATION
| 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)
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| Project Period (FY) |
1997 – 1998
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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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