論文 - 詳細
| RRC ID | 6801 |
|---|---|
| 著者 | Yamaguchi U, Honda K, Satow R, Kobayashi E, Nakayama R, Ichikawa H, Shoji A, Shitashige M, Masuda M, Kawai A, Chuman H, Iwamoto Y, Hirohashi S, Yamada T. |
| タイトル | Functional genome screen for therapeutic targets of osteosarcoma. |
| ジャーナル | Cancer Sci |
| Abstract |
Osteosarcoma (OS) is the most frequent primary malignant bone tumor of children and young adults. Although the introduction of combined neoadjuvant chemotherapy has markedly improved survival, the outcome of OS patients with distant metastasis and/or poor response to chemotherapy is still unsatisfactory. Therefore there is a need to develop new therapeutic agents that suppress OS cell proliferation with higher efficacy. The protein kinases are a family of genes that play critical roles in various signaling pathways. Some cancer cells show addiction to constitutive activation of certain signaling pathways for proliferation and survival. To identify new drug targets for OS, we screened a panel of small interfering RNAs (siRNAs) that target 691 genes encoding human protein kinases and related proteins. We found that different constructs of siRNA specifically targeting polo-like 1 kinase (PLK1) significantly caused mitotic cell cycle arrest and subsequent apoptotic cell death in a variety of OS cell lines. siRNA targeting PLK1 also suppressed the growth of OS xenografts established in immunodeficient mice. Recently, phase I clinical trials of PLK1 chemical inhibitors have been reported. Our results indicate that PLK1 is a promising molecular target for pharmacologic intervention in OS. |
| 巻・号 | 100(12) |
| ページ | 2268-74 |
| 公開日 | 2009-12-1 |
| DOI | 10.1111/j.1349-7006.2009.01310.x |
| PII | CAS1310 |
| PMID | 19725836 |
| MeSH | Animals Bone Neoplasms / genetics Bone Neoplasms / therapy* Cell Cycle Proteins / antagonists & inhibitors* Cell Cycle Proteins / genetics Cell Line, Tumor Humans Male Mice Mice, Inbred BALB C Osteosarcoma / genetics Osteosarcoma / therapy* Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / genetics Proto-Oncogene Proteins / antagonists & inhibitors* Proto-Oncogene Proteins / genetics RNA, Small Interfering / therapeutic use* |
| IF | 4.966 |
| 引用数 | 26 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HS-Os-1(RCB2229) NOS-1(RCB1032) HuO-3N1(RCB2104) |