論文 - 詳細
| RRC ID | 43682 |
|---|---|
| 著者 | Eguchi R, Kubo S, Takeda H, Ohta T, Tabata C, Ogawa H, Nakano T, Fujimori Y. |
| タイトル | Deficiency of Fyn protein is prerequisite for apoptosis induced by Src family kinase inhibitors in human mesothelioma cells. |
| ジャーナル | Carcinogenesis |
| Abstract |
Malignant mesothelioma is an aggressive tumor arising from mesothelial cells of serous membranes. Src family kinases (SFKs) have a pivotal role in cell adhesion, proliferation, survival and apoptosis. Here, we examined the effect of SFK inhibitors in NCI-H2052, ACC-MESO-4 and NCI-H28 cells, mesothelioma cell lines and Met5A, a human non-malignant mesothelial cell line. We found that PP2, a selective SFK inhibitor, inhibited SFK activity and induced apoptosis mediated by caspase-8 in NCI-H28 but not Met5A, NCI-H2052 and ACC-MESO-4 cells. Src, Yes, Fyn and Lyn protein, which are members of the SFK, were expressed in these cell lines, whereas NCI-H28 cells were deficient in Fyn protein. Small interfering RNA (siRNA) targeting Fyn facilitated PP2-induced apoptosis mediated by caspase-8 in NCI-H2052 and ACC-MESO-4 cells. PP2 reduced Lyn protein levels and suppressed SFK activity in all mesothelioma cell lines. Lyn siRNA induced caspase-8 activation and apoptosis in NCI-H28 cells but not in NCI-H2052 and ACC-MESO-4 cells. However, double RNA interference knockdown of Fyn and Lyn induced apoptosis accompanied by caspase-8 activation in NCI-H2052 and ACC-MESO-4 cells. Dasatinib, an inhibitor of multi-tyrosine kinases including SFK, also inhibited SFK activity and induced reduction of Lyn protein levels, caspase-8 activation and apoptosis in NCI-H28 cells but not in other cell lines. Present study suggests that SFK inhibitors induce caspase-8-dependent apoptosis caused by reduction of Lyn protein in Fyn-deficient mesothelioma cells. |
| 巻・号 | 33(5) |
| ページ | 969-75 |
| 公開日 | 2012-5-1 |
| DOI | 10.1093/carcin/bgs109 |
| PII | bgs109 |
| PMID | 22354875 |
| MeSH | Apoptosis / drug effects Apoptosis / physiology* Caspase 8 / genetics Caspase 8 / metabolism Cell Line, Tumor Humans Mesothelioma / genetics Mesothelioma / metabolism* Mesothelioma / pathology* Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-fyn / deficiency* Proto-Oncogene Proteins c-fyn / genetics Proto-Oncogene Proteins c-fyn / metabolism Proto-Oncogene Proteins c-yes / genetics Proto-Oncogene Proteins c-yes / metabolism Pyrimidines / pharmacology RNA, Messenger / genetics RNA, Small Interfering / genetics Signal Transduction / drug effects Signal Transduction / genetics Transcription, Genetic / drug effects src-Family Kinases / antagonists & inhibitors* src-Family Kinases / genetics src-Family Kinases / metabolism* |
| IF | 4.603 |
| 引用数 | 17 |
| 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 | 1 |
| 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 | |
| ヒト・動物細胞 | ACC-MESO-4(RCB2293) |