論文 - 詳細
| RRC ID | 41598 |
|---|---|
| 著者 | Yatabe N, Kyo S, Kondo S, Kanaya T, Wang Z, Maida Y, Takakura M, Nakamura M, Tanaka M, Inoue M. |
| タイトル | 2-5A antisense therapy directed against human telomerase RNA inhibits telomerase activity and induces apoptosis without telomere impairment in cervical cancer cells. |
| ジャーナル | Cancer Gene Ther |
| Abstract |
Human telomerase RNA (hTR), an important component of telomerase, is a possible target of telomerase-based cancer gene therapy. The present study was undertaken to assess the efficacy of antisense hTR therapy using newly developed 2-5A (5'-phosphorylated 2'-5'-linked oligoadenylate)-linked oligonucleotides against cervical cancer cells. ME180 and SiHa cells were treated with 2-5A-linked antisense hTR designed to complement the region of hTR between residues 76 and 94. The hTR expression, telomerase activity, cell viability, and apoptosis were then examined. The 2-5A anti-hTR effectively degraded hTR and inhibited telomerase activity. The 2-5A mutant anti-hTR and the anti-hTR without 2-5A were not capable of inhibiting telomerase activity. Inhibition of telomerase by 2-5A anti-hTR rapidly decreased cell viability only in telomerase-positive cells within 3-6 days after the treatment, when telomere length has not yet been shortened. This inhibition was associated with apoptosis, possibly through activation of caspase family members. These findings suggest that 2-5A-linked antisense-hTR therapy has a potent telomerase-inhibitory effect associated with a cytocidal effect from caspase-induced apoptosis, and may therefore be a potential tool in telomerase-based gene therapy against cervical cancers. |
| 巻・号 | 9(7) |
| ページ | 624-30 |
| 公開日 | 2002-7-1 |
| DOI | 10.1038/sj.cgt.7700479 |
| PMID | 12082463 |
| MeSH | Apoptosis* Blotting, Southern Cell Survival Female Flow Cytometry Genetic Therapy / methods* Humans Oligonucleotides / pharmacology Oligonucleotides, Antisense / pharmacology* RNA / metabolism* Reverse Transcriptase Polymerase Chain Reaction Telomerase / antagonists & inhibitors* Telomerase / genetics* Telomere / metabolism Time Factors Transfection Tumor Cells, Cultured Uterine Cervical Neoplasms / genetics* Uterine Cervical Neoplasms / therapy |
| IF | 4.534 |
| 引用数 | 42 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL BIOTECHNOLOGY & APPLIED MICROBIOLOGY ONCOLOGY GENETICS & HEREDITY |
| 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 | 2 |
| 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 | SUSM-1(RCB0174) VA-13(RCB0251) |