論文 - 詳細
| RRC ID | 43124 |
|---|---|
| 著者 | Morikawa T, Sugiyama A, Kume H, Ota S, Kashima T, Tomita K, Kitamura T, Kodama T, Fukayama M, Aburatani H. |
| タイトル | Identification of Toll-like receptor 3 as a potential therapeutic target in clear cell renal cell carcinoma. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:Renal cell carcinoma (RCC) is one of the most drug-refractory cancers. The aim of this study is to discover a novel therapeutic target molecule for clear cell RCC (CCRCC), which accounts for the majority of RCC. EXPERIMENTAL DESIGN:Gene expression profiles of 27 CCRCCs and 9 normal kidney tissues as well as 15 various adult normal tissues were examined by Affymetrix U133 Plus 2.0 arrays. Among the 34 genes specifically up-regulated in CCRCC, overexpression of Toll-like receptor 3 (TLR3) mRNA and its protein was validated by quantitative reverse transcription-PCR, immunoblot, and immunohistochemistry. The effects of TLR3 signaling on in vitro cell growth were examined. RESULTS:TLR3 gene was highly expressed in CCRCC, with only limited expression in a panel of normal tissues. On immunohistochemical analysis using a monoclonal antibody against TLR3, overexpression of TLR3 was observed in 139 of 189 (73.5%) cases of CCRCC as well as in lung metastatic CCRCC (6 of 8), whereas TLR3 expression was entirely absent in chromophobe RCC (0 of 8). Polyinosinic-polycytidilic acid, a TLR3 ligand, exerted a growth-inhibitory effect against RCC cells in a TLR3-dependent manner. Moreover, a combination of polyinosinic-polycytidilic acid and IFNalpha exerted a synergistic growth-inhibitory effect against Caki-1 RCC cells. CONCLUSIONS:This is the first report that TLR3 is overexpressed in CCRCC. These observations suggest that TLR3 pathway may represent a novel therapeutic target in CCRCC. |
| 巻・号 | 13(19) |
| ページ | 5703-9 |
| 公開日 | 2007-10-1 |
| DOI | 10.1158/1078-0432.CCR-07-0603 |
| PII | 13/19/5703 |
| PMID | 17908959 |
| MeSH | Aged Antineoplastic Agents / pharmacology* Apoptosis Carcinoma, Renal Cell / drug therapy* Carcinoma, Renal Cell / metabolism* Drug Design Female Gene Expression Profiling* Gene Expression Regulation, Neoplastic* Humans Interferon Inducers / pharmacology Kidney Neoplasms / drug therapy* Kidney Neoplasms / metabolism* Male Middle Aged Poly I-C / pharmacology Toll-Like Receptor 3 / metabolism Toll-Like Receptor 3 / physiology* |
| IF | 10.107 |
| 引用数 | 61 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | OS-RC-2(RCB0735) TUHR10TKB(RCB1275) TUHR14TKB(RCB1383) |