| pubmed-article:19418558 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0162508 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C1882695 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C1326912 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0031727 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0919432 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C1707719 | lld:lifeskim |
| pubmed-article:19418558 | lifeskim:mentions | umls-concept:C0301625 | lld:lifeskim |
| pubmed-article:19418558 | pubmed:issue | 6 | lld:pubmed |
| pubmed-article:19418558 | pubmed:dateCreated | 2009-6-3 | lld:pubmed |
| pubmed-article:19418558 | pubmed:abstractText | Transforming growth factor beta (TGF-beta) signaling involves both tumor-suppression and oncogenesis. TGF-beta activates the TGF-beta type I receptor (TbetaRI) and c-Jun N-terminal kinase (JNK), which differentially phosphorylate the mediator Smad3 to become COOH-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TbetaRI-dependent pSmad3C transmits a tumor-suppressive TGF-beta signal, while JNK-dependent pSmad3L promotes carcinogenesis in human chronic liver disorders. The aim of this study is to elucidate how SP600125, a JNK inhibitor, affected rat hepatocellular carcinoma (HCC) development, while focusing on the domain-specific phosphorylation of Smad3. The rats received subcutaneous injections of either SP600125 or vehicle 11 times weekly together with 100 ppm N-diethylnitrosamine (DEN) administration for 56 days and were sacrificed in order to evaluate HCC development 28 days after the last DEN administration. The number of tumor nodules greater than 3 mm in diameter and the liver weight/body weight ratio were significantly lower in the SP600125-treated rats than those in the vehicle-treated rats (7.9 +/- 0.8 versus 17.7 +/- 0.9: P < 0.001; 6.3 +/- 1.2 versus 7.1 +/- 0.2%: P < 0.05). SP600125 significantly prolonged the median survival time in rats with DEN-induced HCC (113 versus 97 days: log-rank P = 0.0018). JNK/pSmad3L/c-Myc was enhanced in the rat hepatocytes exposed to DEN. However, TbetaRI/pSmad3C/p21(WAF1) was impaired as DEN-induced HCC developed and progressed. The specific inhibition of JNK activity by SP600125 suppressed pSmad3L/c-Myc in the damaged hepatocytes and enhanced pSmad3C/p21(WAF1), acting as a tumor suppressor in normal hepatocytes. CONCLUSION: Administration of SP600125 to DEN-treated rats shifted hepatocytic Smad3-mediated signal from oncogenesis to tumor suppression, thus suggesting that JNK could be a therapeutic target of human HCC development and progression. | lld:pubmed |
| pubmed-article:19418558 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19418558 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19418558 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19418558 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19418558 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:19418558 | pubmed:issn | 1527-3350 | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:COXP JPJ | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:MatsuzakiKoic... | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:HatanoEtsuroE | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:YagiShintaroS | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:TamakiNobuyuk... | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:UemotoShinjiS | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:KitamuraKojiK | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:MurataMikiM | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:TadaMasaharuM | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:NaritaMasatoM | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:NagataHiromit... | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:AsechiHiroyuk... | lld:pubmed |
| pubmed-article:19418558 | pubmed:author | pubmed-author:YanagidaAtsuk... | lld:pubmed |
| pubmed-article:19418558 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19418558 | pubmed:volume | 49 | lld:pubmed |
| pubmed-article:19418558 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19418558 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19418558 | pubmed:pagination | 1944-53 | lld:pubmed |
| pubmed-article:19418558 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
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| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:meshHeading | pubmed-meshheading:19418558... | lld:pubmed |
| pubmed-article:19418558 | pubmed:year | 2009 | lld:pubmed |
| pubmed-article:19418558 | pubmed:articleTitle | Inhibition of c-Jun NH2-terminal kinase switches Smad3 signaling from oncogenesis to tumor- suppression in rat hepatocellular carcinoma. | lld:pubmed |
| pubmed-article:19418558 | pubmed:affiliation | Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan. | lld:pubmed |
| pubmed-article:19418558 | pubmed:publicationType | Journal Article | lld:pubmed |
