2000 Fiscal Year Final Research Report Summary
Analyses of TGF-β Signal Transduction Mechanisms in Hepatocellular Carcinoma and Applications for its Treatment.
| 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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| Keywords | Hepatocellular Carcinoma / TGF-β / Smad |
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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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Research Products
(12 results)
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[Publications] Matsuzaki K, Date M., Furukawa F., Tahashi Y., Matsushita M., Sugano Y., Yamashiki N., Nakagawa T., Seki T., Nishizawa M., Fujisawa J., Inoue K.: "Regulatory Mechanisms for TGF-β as Autocrine Inhibitor in Human Hepatocellular Carcinoma : Implications for Roles of Smads in Its Growth."Hepatology.. 32. 218-227 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsuzaki K, Date M., Furukawa F., Tahashi Y., Matsushita M., Sakitani K., Yamashiki N., Seki T., Saito H., Nishizawa M., Fujisawa J., Inoue K.: "Autocrine Stimulatory Mechanism by TGF-β in Human Hepatocellular Carcinoma."Cancer Res.. 60. 1394-1402 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Matsushita M, Matsuzaki K, Date M, Watanabe T, Shibano K, Nakagawa T, Yanagitani S, Amoh Y, Ogata N, Yamamoto C, Kubota T, Seki T, Inokuchi H, Nishizawa M, Takada H, Sawamura T, Okamura A, Inoue K.: "Down-regulation of TGF-β receptors in Human Colorectal Cancer : Implications for Cancer Development."British Journal of Cancer. 80 (1/2). 194-205 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Date M., Matsuzaki K., Matsushita M., Sakitani K., Okajima A., Shibano K., Yamamoto C., Ogata N., Okumura T., Seki T., Kubota T., Kan M., McKeehan W.L.and Inoue K.: "Differential Expression of Transforming Growth Factor-β Receptors in Hepatocytes and Nonparenchymal Cells of Rat Liver Injury"Journal of Hepatology. 28. 572-581 (1998)
Description
「研究成果報告書概要(欧文)」より
