| Project/Area Number |
11670546
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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 |
Gastroenterology
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| Research Institution | Kansai Medical University |
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Principal Investigator |
MATSUZAKI Koichi Kansai Medical University Third Department of Internal Medicine Assistant Professor, 医学部, 講師 (70278638)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAHASHI Yoshitsugu Kansai Medical University Third Department of Internal Medicine Research Assistant, 医学部, 助手 (70247930)
SEKI Toshihito Kansai Medical University Third Department of Internal Medicine Associate Professor, 医学部, 助教授 (70163087)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Hepatocellular Carcinoma / TGF-β / Smad / TGF-β受容体 / アクチビン |
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| Research Abstract |
To clarify the mechanism of resistance to the anti-proliferative effect of TGF-b in human HCC cells, we studied the stimulatory mechanism by tumor-derived TGF-β using HCC-M and HCC-T cell lines. In these cells, tumor-derived TGF-β accelerated their proliferation. Smad 2 was constitutively activated by the autocrine mechanism. This constitutive activation of Smad 2 was, at least in part, due to the lack of induction of antagonistic Smads by TGF-β (Cancer Res. 2000 ; 60 : 1394-1402). Furthermore, we investigated regulatory mechanisms for TGF-β as an autocrine inhibitor using HuH-7 and HepG2 cells. The study demonstrated that HuH-7 and HepG2 cells exhibited only a limited growth inhibitory response to TGF-β in comparison with hepatocytes, because tumor-derived TGF-β induced antagonistic Smad 7, and Smad 7 limited the basal activation levels of R-Smads (Hepatology 2000 ; 32 : 218-227).
We also showed that Down-regulation of TGF-β receptor occurred in hepatocytes after chemical insult and TGF-β could not transduce its anti-proliferative signal. Recovery of TGF-β receptor expression causes the signal to transduce to the nucleus at 72 hr. In HSC, whenever TGF-β is increased, TGF-β can transduce its signal for fibronectin production via its receptor, because signaling receptors are expressed constantly (Gut 2000 ; 46 : 719-724, J of Hepatology 2000 ; 32 : 251-260, J of Hepatology 1998 ; 28 : 572-581).
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