| Critical role of cyclin B1/Cdc2 up-regulation in the induction of mitotic prometaphase arrest in human breast cancer cells treated with 2-methoxyestradiol. | |
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MedLine Citation:
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PMID: 22580043 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Earlier studies showed that 2-methoxyestradiol (2ME(2)), an endogenous nonpolar metabolite of estradiol-17β, is a strong inducer of G(2)/M cell cycle arrest (based on analysis of cellular DNA content) in human cancer cell lines. The present study sought to investigate the molecular mechanism underlying 2ME(2)-induced cell cycle arrest. We found that 2ME(2) can selectively induce mitotic prometaphase arrest, but not G(2) phase arrest, in cultured MDA-MB-435s and MCF-7 human breast cancer cells. During the induction of prometaphase arrest, there is a time-dependent initial up-regulation of cyclin B1 and Cdc2 proteins, occurring around 12-24h. The strong initial up-regulation of cyclin B1 and Cdc2 matches in timing the 2ME(2)-induced prometaphase arrest. The 2ME(2)-induced prometaphase arrest is abrogated by selective knockdown of cyclin B1 and Cdc2, or by pre-treatment of cells with roscovitine, an inhibitor of cyclin-dependent kinases, or by co-treatment of cells with cycloheximide, a protein synthesis inhibitor that was found to suppress the early up-regulation of cyclin B1 and Cdc2. In addition, we provided evidence showing that MAD2 and JNK1 are important upstream mediators of 2ME(2)-induced up-regulation of cyclin B1 and Cdc2 as well as the subsequent induction of mitotic prometaphase arrest. In conclusion, treatment of human cancer cells with 2ME(2) causes up-regulation of cyclin B1 and Cdc2, which then mediate the induction of mitotic prometaphase arrest. |
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Authors:
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Hye Joung Choi; Bao Ting Zhu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-10 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1823 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-07-03 Completed Date: 2013-02-21 Revised Date: 2013-04-22 |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1306-15 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier B.V. All rights reserved. |
Affiliation:
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Department of Pharmacology, University of Kansas Medical Center, Kansas City, KS, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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pharmacology* Breast Neoplasms Calcium-Binding Proteins / metabolism Cell Cycle Proteins / genetics, metabolism Cell Line, Tumor Cell Nucleus Shape / drug effects Cyclin B / genetics*, metabolism Cyclin B1 / genetics*, metabolism Estradiol / analogs & derivatives*, pharmacology Female G2 Phase Cell Cycle Checkpoints / drug effects Gene Knockdown Techniques Humans Mitogen-Activated Protein Kinase 8 / metabolism Prometaphase / drug effects* RNA Interference Repressor Proteins / metabolism Up-Regulation / drug effects* |
| Grant Support | |
ID/Acronym/Agency:
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CA-97109/CA/NCI NIH HHS; P20 RR021940/RR/NCRR NIH HHS; P20RR021940/RR/NCRR NIH HHS; R01 CA097109/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/CCNB1 protein, human; 0/CDC2 protein, human; 0/Calcium-Binding Proteins; 0/Cell Cycle Proteins; 0/Cyclin B; 0/Cyclin B1; 0/MAD2L1 protein, human; 0/Repressor Proteins; 50-28-2/Estradiol; 6I2QW73SR5/2-methoxyestradiol; EC 2.7.11.24/Mitogen-Activated Protein Kinase 8 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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