論文 - 詳細
| RRC ID | 41644 |
|---|---|
| 著者 | Tang X, Yano T, Osuga Y, Matsumi H, Yano N, Xu J, Wada O, Koga K, Kugu K, Tsutsumi O, Schally AV, Taketani Y. |
| タイトル | Cellular mechanisms of growth inhibition of human epithelial ovarian cancer cell line by LH-releasing hormone antagonist Cetrorelix. |
| ジャーナル | J Clin Endocrinol Metab |
| Abstract |
We investigated the direct effects of LH-releasing hormone (LH-RH) antagonist, Cetrorelix, on the growth of HTOA human epithelial ovarian cancer cell line. RT-PCR revealed the expression of mRNA for LH-RH and its receptor in HTOA cells. Cetrorelix, at concentrations between 10(-9) and 10(-5) M, exerted a dose-dependent antiproliferative action on HTOA cells, as measured by 5-bromo-2'-deoxyuridine incorporation into DNA. Flow cytometric analysis indicated that Cetrorelix, at 10(-5) M, arrested cell cycle in HTOA cells, at G1 phase, after 24 h of treatment. Western blot analysis of cell cycle-regulatory proteins demonstrated that treatment with Cetrorelix (10(-5) M) for 24 h did not change the steady-state levels of cyclin D1, cyclin E, and cyclin-dependent kinase (Cdk)4 but decreased the levels of cyclin A and Cdk2. The protein levels of p21 (a Cdk inhibitor) and p53 (a suppressor of tumor cell growth and a positive regulator for p21 expression) were increased by Cetrorelix, but the levels of p27 (a Cdk inhibitor) did not change significantly. Flow cytometric analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine 5-triphosphate nick end labeling staining demonstrated that Cetrorelix (10(-5) M) induced apoptosis in HTOA cells. In conclusion, Cetrorelix directly inhibits the proliferation of human epithelial ovarian cancer cells through mechanisms mediated by LH-RH receptor and involving multiple events in cell cycle progression, including G1 phase cell cycle arrest coupled with down-regulation of cyclin A-Cdk2 complex levels, presumably attributable to an up-regulation of p53 and p21 protein levels and apoptosis. |
| 巻・号 | 87(8) |
| ページ | 3721-7 |
| 公開日 | 2002-8-1 |
| DOI | 10.1210/jcem.87.8.8726 |
| PMID | 12161501 |
| MeSH | Apoptosis / drug effects Cell Division / drug effects DNA / biosynthesis Epithelial Cells / cytology Epithelial Cells / drug effects Female Gene Expression Regulation, Neoplastic / drug effects Genes, cdc / drug effects Gonadotropin-Releasing Hormone / analogs & derivatives* Gonadotropin-Releasing Hormone / antagonists & inhibitors* Gonadotropin-Releasing Hormone / pharmacology* Hormone Antagonists / pharmacology* Humans Ovarian Neoplasms* RNA, Messenger / analysis Receptors, LHRH / genetics Tumor Cells, Cultured / cytology Tumor Cells, Cultured / drug effects |
| IF | 5.399 |
| 引用数 | 43 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| 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 | HTOA(RCB0692) |