| Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway. | |
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MedLine Citation:
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PMID: 16287090 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Resistance to anticancer drugs is the major problem in the treatment of many advanced cancers, including androgen-independent prostate cancer. Recently, increased expression of Id-1, a basic helix-loop-helix protein, is reported in several types of advanced cancer. It is suggested that high expression of Id-1 may provide an advantage for cancer cell survival and inactivation of Id-1 may be able to increase cancer cells' susceptibility to apoptosis. To test this hypothesis, in this study, by using RNA interfering technology, we inactivated the Id-1 gene in 2 androgen-independent prostate cancer cell lines, DU145 and PC3, and investigated whether downregulation of Id-1 could lead to increased sensitivity to a commonly used anticancer drug, taxol. By using colony forming assay and MTT assay, we found that inactivation of Id-1 resulted in both decreased colony forming ability and cell viability in prostate cancer cells, after taxol treatment. In addition, the si-Id-1-induced sensitization to taxol was associated with activation of apoptosis pathway, which is demonstrated by increased apoptotic index, DNA laddering, sub-G1 phase of the cell cycle, as well as cleaved-PARP and Caspase 3. Furthermore, c-Jun N-terminal kinase (JNK), one of the common pathways responsible for taxol-induced apoptosis, was also activated in the si-Id-1 transfected cells. Inhibition of JNK activity by a specific inhibitor, SP600125, blocked the si-Id-1-induced sensitivity to taxol. These results indicate that increased Id-1 expression in prostate cancer cells may play a protective role against apoptosis, and downregulation of Id-1 may be a potential target to increase sensitivity of taxol-induced apoptosis in prostate cancer cells. |
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Authors:
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Xiaomeng Zhang; Ming-Tat Ling; Xianghong Wang; Y C Wong |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 118 ISSN: 0020-7136 ISO Abbreviation: Int. J. Cancer Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-02-21 Completed Date: 2006-04-18 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 2072-81 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2005 Wiley-Liss, Inc. |
Affiliation:
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Cancer Biology Group, Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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pharmacology* Apoptosis Cell Survival Down-Regulation Drug Resistance, Neoplasm Enzyme Activation Gene Expression Profiling Humans Inhibitor of Differentiation Protein 1 / biosynthesis*, physiology MAP Kinase Kinase 4 / metabolism* Male Paclitaxel / pharmacology* Prostatic Neoplasms / pathology* RNA Interference* Tumor Cells, Cultured Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Inhibitor of Differentiation Protein 1; 33069-62-4/Paclitaxel; EC 2.7.12.2/MAP Kinase Kinase 4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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