論文 - 詳細
| RRC ID | 12772 |
|---|---|
| 著者 | Ehata S, Hanyu A, Fujime M, Katsuno Y, Fukunaga E, Goto K, Ishikawa Y, Nomura K, Yokoo H, Shimizu T, Ogata E, Miyazono K, Shimizu K, Imamura T. |
| タイトル | Ki26894, a novel transforming growth factor-beta type I receptor kinase inhibitor, inhibits in vitro invasion and in vivo bone metastasis of a human breast cancer cell line. |
| ジャーナル | Cancer Sci |
| Abstract |
Transforming growth factor (TGF)-beta signaling has been shown to promote tumor growth and metastasis in advanced cancer. Use of inhibitors of TGF-beta signaling may thus be a novel strategy for treatment of patients with such cancers. In this study, we investigated the effects of a novel TGF-beta type I receptor (TbetaR-I) kinase inhibitor, Ki26894, on bone metastasis of a highly bone-metastatic variant of human breast cancer MDA-MB-231 cells, termed MDA-MB-231-5a-D (MDA-231-D). Ki26894 blocked TGF-beta signaling in MDA-231-D cells, as detected by suppression of phosphorylation of Smad2 and inhibition of TGF-beta-responsive reporter activity. Moreover, Ki26894 decreased the motility and the invasion of MDA-231-D cells induced by TGF-beta in vitro. Ki26894 also suppressed transcription of plasminogen activator inhibitor-1 (PAI-1), parathyroid hormone-related protein (PTHrP), and interleukin-11 (IL-11) mRNA of MDA-231-D cells, which were stimulated by TGF-beta. X-ray radiography revealed that systemic Ki26894 treatment initiated 1 day before the inoculation of MDA-231-D cells into the left ventricle of BALB/cnu/nu female mice resulted in decreased bone metastasis of breast cancer cells. Moreover, Ki26894 prolonged the survival of mice inoculated with MDA-231-D cells compared to vehicle-treated mice. These findings suggest that TbetaR-I kinase inhibitors such as Ki26894 may be useful for blocking the progression of advanced cancers. |
| 巻・号 | 98(1) |
| ページ | 127-33 |
| 公開日 | 2007-1-1 |
| DOI | 10.1111/j.1349-7006.2006.00357.x |
| PII | CAS357 |
| PMID | 17129361 |
| MeSH | Activin Receptors, Type I / drug effects Activin Receptors, Type I / pharmacokinetics* Animals Antineoplastic Agents / pharmacology* Bone Neoplasms / drug therapy* Bone Neoplasms / secondary Female Humans Immunoblotting In Vitro Techniques Mammary Neoplasms, Experimental / drug therapy* Mammary Neoplasms, Experimental / pathology* Mice Neoplasm Invasiveness / prevention & control Neoplasm Metastasis / prevention & control* Protein Kinase Inhibitors / pharmacology* Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type I Receptors, Transforming Growth Factor beta / drug effects Reverse Transcriptase Polymerase Chain Reaction |
| IF | 4.966 |
| 引用数 | 138 |
| WOS 分野 | ONCOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04394) CS-CDF-CG-PRE (RDB04379) |