論文 - 詳細
| RRC ID | 42289 |
|---|---|
| 著者 | Shao RX, Otsuka M, Kato N, Taniguchi H, Hoshida Y, Moriyama M, Kawabe T, Omata M. |
| タイトル | Acyclic retinoid inhibits human hepatoma cell growth by suppressing fibroblast growth factor-mediated signaling pathways. |
| ジャーナル | Gastroenterology |
| Abstract |
BACKGROUND & AIMS:Hepatocellular carcinoma (HCC) is one of the most common human malignancies. Its high mortality rate is mainly a result of high intrahepatic recurrence. The novel synthetic retinoid acyclic retinoid (ACR) has been reported to prevent the recurrence of human HCC after surgical resection of primary tumors, but the molecular mechanisms underlying its effects remain to be elucidated. In this study, we clarified the molecular targets of ACR. METHODS:The inhibitory effects by ACR on growth were examined. Intracellular signaling induced by ACR was comprehensively studied by a reporter assay. Gene expression changes by ACR were examined using a microarray. From these results, a candidate signaling pathway modulated by ACR was determined and whether antagonizing this pathway reverses the effect was examined. RESULTS:We show that ACR inhibits the growth of HCC cells through the down-regulation of fibroblast growth factor (FGF) receptor 3 expression and FGF-mediated signaling, which in turn suppresses the activity of Rho and serum response factor-mediated transcription. Conversely, overexpression of the active form of FGF receptor 3 or the addition of FGF reverses the ACR-mediated inhibition of growth. In addition, silencing the FGF receptor 3 gene by RNA interference inhibits cell growth. CONCLUSIONS:These studies show that ACR is a potent inhibitor of FGF signaling and that selective blocking of the FGF-mediated pathway could be a promising therapeutic approach for the management of patients with HCC. |
| 巻・号 | 128(1) |
| ページ | 86-95 |
| 公開日 | 2005-1-1 |
| DOI | 10.1053/j.gastro.2004.09.077 |
| PII | S0016508504017469 |
| PMID | 15633126 |
| MeSH | Antineoplastic Agents / pharmacology* Antineoplastic Agents / therapeutic use Carcinoma, Hepatocellular / drug therapy* Carcinoma, Hepatocellular / metabolism Cell Line, Tumor Cell Proliferation / drug effects Down-Regulation / drug effects Fibroblast Growth Factors / drug effects* Fibroblast Growth Factors / metabolism Gene Expression / drug effects Humans Liver Neoplasms / drug therapy* Liver Neoplasms / metabolism Neoplasm Recurrence, Local / metabolism Oligonucleotide Array Sequence Analysis Protein-Tyrosine Kinases / drug effects Receptor, Fibroblast Growth Factor, Type 3 Receptors, Fibroblast Growth Factor / drug effects Signal Transduction / drug effects Tretinoin / analogs & derivatives* Tretinoin / pharmacology* Tretinoin / therapeutic use rho GTP-Binding Proteins / drug effects |
| IF | 17.373 |
| 引用数 | 30 |
| WOS 分野 | GASTROENTEROLOGY & HEPATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | Hep G2 HuH-7(RCB1366) |