2001 Fiscal Year Final Research Report Summary
TGF-b mediated growth suppression and p27 laplimobuced motibry in HCC
| Project/Area Number |
11670541
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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 | Tokyo Woman's Med. Univ. Instifute of Gostroenterolosy |
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Principal Investigator |
NAGAHARA Hikaru Tokyo Woman's Med. Univ. Associate Professor, 医学部, 講師 (50172549)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Apoptosis / TGF-b / cell cycle arrest / ERK / Akt / motility / hepatocellular carcinoma (HCC) |
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| Research Abstract |
Primary hepatocytes and hepatocellular carcinoma (HCC) are sensitive to TGF-b treatment, resulting in apoptosis. We wish to elucidate molecular mechanisms of TGF-b mediated apoptosis and the interaction between TGF-b and other signaling pathways that are able to abrogate apoptosis. Huh2, Huh7, Hep3B and HepG2 were treated with 0.5〜2ng/ml of TGF-b and analyzed sub-Gi population as an apoptotic population by FACS. To inhibit apoptosis, cells were pretreated with 25〜50ng/ml of EGF or 3Ong/ml of HGF1hr before TGF-b addition. Furthermore, ERK and Akt signaling pathways, candidates for downstream targets of EGF or HGF, were specifically inhibited by PD98059 and LY294002, respectively. While TGF-b induced apoptosis in Huh2, Huh7 and Hep3b, HepG2 cells were resistant to the treatment. Pretreatment with EGF and HGF efficiently rescued cells from apoptosis, however, PD and LY addition 1hr before EGF treatment resulted in re-induction of apoptosis. These results suggest that EGF and HGF inhibit TGF-b induced apoptosis by activation of both ERK and Akt signals. We hypothesized that PD and LY treatments brought about apoptosis by TGF-b even in HepG2 cells as well as other 3 cell lines. Expectantly HepG2 cells led to apoptosis with dose dependent manner of PD and LY. Together, TGF-b mediated apoptosis are a general phenomenon in HCC, and both ERK and Akt activation produce inhibitory signals against apoptosis.
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Research Products
(8 results)
