論文 - 詳細
| RRC ID | 1199 |
|---|---|
| 著者 | Horiguchi-Yamada J, Fukumi S, Saito S, Nakayama R, Iwase S, Yamada H. |
| タイトル | DNA topoisomerase II inhibitor, etoposide, induces p21WAF1/CIP1 through down-regulation of c-Myc in K562 cells. |
| ジャーナル | Anticancer Res |
| Abstract |
BACKGROUND:Anticancer agents modulate gene expression and these changes are essential for tumor cell killing. To investigate the mechanism by which etoposide acts as an anticancer agent, the relationship between p21WAF1/CIP1 (p21) and c-Myc was studied. MATERIALS AND METHODS:K562 cells with and without ectopic c-Myc expression were studied. Apoptosis was detected using propidium iodide and Hoechst 33342 double staining. The c-Myc and p21 levels were studied by RT-PCR and immunoblot. The p21 promoter (from -205 to +67) was investigated by the luciferase reporter gene assay. RESULTS:Ectopic c-Myc-expressing K562 (K562/c-Myc) cells showed more extensive apoptosis than K562 cells after continuous exposure to 200 microM etoposide for 24 hours. During this treatment, p21 expression was not observed in K562/c-Myc cells, and the expression of c-Myc and p21 was mutually exclusive. Etoposide activated the p21 promoter in a concentration-dependent manner, and etoposide-induced luciferase activity was suppressed by co-transfection of c-Myc. CONCLUSION:p21 promoter activity was repressed by c-Myc in proliferating K562 cells, and detoposide-induced down-regulation of c-Myc released this suppression, resulting in the induction of p21. |
| 巻・号 | 22(6C) |
| ページ | 3827-32 |
| 公開日 | 2002-1-1 |
| PMID | 12553001 |
| MeSH | Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects Base Sequence Cyclin-Dependent Kinase Inhibitor p21 Cyclins / antagonists & inhibitors Cyclins / biosynthesis* Cyclins / genetics Down-Regulation / drug effects Enzyme Inhibitors / pharmacology* Etoposide / pharmacology* Gene Expression Regulation, Neoplastic / drug effects* Genes, myc / drug effects Genes, myc / genetics Humans K562 Cells / drug effects* K562 Cells / metabolism K562 Cells / physiology Molecular Sequence Data Promoter Regions, Genetic Proto-Oncogene Proteins c-myc / biosynthesis* Proto-Oncogene Proteins c-myc / genetics Topoisomerase II Inhibitors* Transcription, Genetic / drug effects |
| IF | 1.994 |
| 引用数 | 10 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | K562(RCB0027) |