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Smoothened as a new therapeutic target for human osteosarcoma
http://hdl.handle.net/10232/19980
http://hdl.handle.net/10232/19980baad5a2b-2d56-490b-866a-821be9cc366f
| 名前 / ファイル | ライセンス | アクション |
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Smoothened as a new therapeutic target for human osteosarcoma.pdf (2.5 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2014-02-10 | |||||
| タイトル | ||||||
| タイトル | Smoothened as a new therapeutic target for human osteosarcoma | |||||
| タイトル言語 | en | |||||
| 著者 |
廣津, 匡隆
× 廣津, 匡隆× 瀬戸口, 啓夫× 松野下, 幸弘× Gao, Hui× 永尾, 宗子× 救仁郷, 修× 小宮, 節郎 |
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| 言語 | ||||||
| 言語 | jpn | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Background: The Hedgehog signaling pathway functions as an organizer in embryonic development. Recent studies have demonstrated constitutive activation of Hedgehog pathway in various types of malignancies. However, it remains unclear how Hedgehog pathway is involved in the pathogenesis of osteosarcoma. To explore the involvement of aberrant Hedgehog pathway in the pathogenesis of osteosarcoma, we investigated the expression and activation of Hedgehog pathway in osteosarcoma and examined the effect of SMOOTHENED (SMO) inhibition. Results: To evaluate the expression of genes of Hedgehog pathway, we performed real-time PCR and immunohistochemistry using osteosarcoma cell lines and osteosarcoma biopsy specimens. To evaluate the effect of SMO inhibition, we did cell viability, colony formation, cell cycle in vitro and xenograft model in vivo. Real-time PCR revealed that osteosarcoma cell lines over-expressed Sonic hedgehog, Indian hedgehog, PTCH1, SMO, and GLI. Realtime PCR revealed over-expression of SMO, PTCH1, and GLI2 in osteosarcoma biopsy specimens. These findings showed that Hedgehog pathway is activated in osteosarcomas. Inhibition of SMO by cyclopamine, a specific inhibitor of SMO, slowed the growth of osteosarcoma in vitro. Cell cycle analysis revealed that cyclopamine promoted G1 arrest. Cyclopamine reduced the expression of accelerators of the cell cycle including cyclin D1, cyclin E1, SKP2, and pRb. On the other hand, p21cip1 wprotein was up-regulated by cyclopamine treatment. In addition, knockdown of SMO by SMO shRNA prevents osteosarcoma growth in vitro and in vivo. Conclusions: These findings suggest that inactivation of SMO may be a useful approach to the treatment of patients with osteosarcoma. |
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| 内容記述言語 | en | |||||
| 収録雑誌名 |
en : Molecular Cancer 巻 9, 号 5, 発行日 2012-01-12 |
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| 作成日 | ||||||
| 日付 | 2012-01-12 | |||||
| 日付タイプ | Issued | |||||
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| 収録物識別子タイプ | EISSN | |||||
| ISSN | 14764598 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| DOI | https://doi.org/10.1186/1476-4598-9-5 | |||||
| 権利 | ||||||
| 権利情報の言語 | en | |||||
| 権利情報 | © 2012 Hirotsu et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 493 | |||||
| 公開者・出版者 | ||||||
| 出版者 | BioMed Central | |||||
| 出版者言語 | en | |||||
