دورية أكاديمية
Insulin-like growth factor binding protein-3 induces G1 cell cycle arrest with inhibition of cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells.
| العنوان: | Insulin-like growth factor binding protein-3 induces G1 cell cycle arrest with inhibition of cyclin-dependent kinase 2 and 4 in MCF-7 human breast cancer cells. |
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| المساهمون: | H.-S. Kim, W. J. Lee, S. W. Lee, H.-W. Chae, D. H. Kim, Y. Oh, Lee, Sun Woo, Chae, Hyun Wook, Kim, Duk Hee, Kim, Ho Seong |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Breast Neoplasms/enzymology, Breast Neoplasms/genetics, Breast Neoplasms/pathology, Cell Line, Tumor, Cell Proliferation/drug effects, Cyclin D1/genetics, Cyclin D1/metabolism, Cyclin-Dependent Kinase 2/antagonists & inhibitors, Cyclin-Dependent Kinase 2/metabolism, Cyclin-Dependent Kinase 4/antagonists & inhibitors, Cyclin-Dependent Kinase 4/metabolism, Cyclin-Dependent Kinase Inhibitor Proteins/metabolism, Ecdysterone/analogs & derivatives, Ecdysterone/pharmacology, Female, G1 Phase*/drug effects, Gene Expression Regulation, Neoplastic/drug effects, Humans, Insulin-Like Growth Factor Binding Protein 3, Insulin-Like Growth Factor Binding Proteins/metabolism, RNA, Messenger/genetics, Messenger/metabolism |
| الوصف: | Insulin-like growth factor binding protein (IGFBP)-3 has been shown to potently inhibit proliferation of various cell types in an insulin-like growth factor (IGF)-independent manner. We have previously shown that IGFBP-3 induces apoptosis in an IGF-independent manner through the activation of caspases involved in a death receptor-mediated pathway in MCF-7 human breast cancer cells. In the present study, we present further evidence that IGFBP-3 inhibits cell proliferation through the induction of cell cycle arrest in the same cell line. Induction of IGFBP-3 in MCF-7 cells inhibited cell proliferation whereas presence of small interfering RNA against IGFBP-3 abolished cell inhibitory effect of IGFBP-3, suggesting that the observed growth inhibition is specific. Flow cytometry analysis showed that induced expression of IGFBP-3 led to an arrest of the cell cycle in G1-S phase. Western immunoblot analysis showed a significant decrease in the levels of the cell cycle-regulated proteins such as cyclin D1, cyclin D3, cyclin E, cyclin A, cyclin-dependent kinase (CDK) 2, CDK4, retinoblastoma protein (pRB), and phosph-pRB, suggesting a possible mechanism for cell cycle arrest by IGFBP-3. Northern blot analysis and real-time quantitative PCR demonstrated a significant decrease in gene expression of cyclin D1. Additional phosphorylation assay showed that IGFBP-3 decreased the phosphorylation activity of CDK2 and CDK4. These results show that cellular production of IGFBP-3 leads to G1 cell cycle arrest with inhibition of CDK2 and CDK4. Taken together, IGFBP-3 exerts its growth inhibitory action through not only induction of apoptosis but also the G1 cell cycle arrest in human breast cancer cells. ; open |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 165~172 |
| اللغة: | unknown |
| تدمد: | 0018-5043 1439-4286 |
| العلاقة: | HORMONE AND METABOLIC RESEARCH; J00999; OAK-2010-00844; https://ir.ymlib.yonsei.ac.kr/handle/22282913/101244Test; T201001884; HORMONE AND METABOLIC RESEARCH, Vol.42(3) : 165-172, 2010 |
| DOI: | 10.1055/s-0029-1243190 |
| الإتاحة: | https://doi.org/10.1055/s-0029-1243190Test https://ir.ymlib.yonsei.ac.kr/handle/22282913/101244Test |
| حقوق: | CC BY-NC-ND 2.0 KR ; https://creativecommons.org/licenses/by-nc-nd/2.0/krTest/ |
| رقم الانضمام: | edsbas.20AC9F3E |
| قاعدة البيانات: | BASE |
| تدمد: | 00185043 14394286 |
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| DOI: | 10.1055/s-0029-1243190 |