| Androgen receptor interacts with telomeric proteins in prostate cancer cells. | |
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MedLine Citation:
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PMID: 20110352 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The telomeric complex, shelterin, plays a critical role in protecting chromosome ends from erosion, and disruption of these complexes can lead to chromosomal instability culminating in cell death or malignant transformation. We reported previously that dominant-negative mutants of one of the telomeric proteins called TIN2 cause death of androgen receptor (AR)-negative but not AR-positive prostate cancer cells, raising the question of a possible role of AR in the structural stability of telomeric complexes. Consistent with this possibility, in the present study, we observed that the AR antagonist Casodex (bicalutamide) disrupted telomeric complexes in AR-positive LNCaP cells but not in AR-negative PC-3 cells. Immunofluorescent studies revealed colocalization of TIN2 and AR. Reciprocal immunoprecipitation studies showed association of AR with telomeric proteins. Furthermore, telomeric proteins were overexpressed in prostate cancer cells compared with normal prostate epithelial cells, and sucrose density gradient analysis showed co-sedimentation of AR with telomeric proteins in a shelterin-like mega complex. Together, these observations suggest an allosteric role of AR in telomere complex stability in prostate cancer cells and suggest that AR-antagonist Casodex-mediated cell death may be due to telomere complex disruption. |
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Authors:
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Sahn-Ho Kim; Michelle Richardson; Kannagi Chinnakannu; V Uma Bai; Mani Menon; Evelyn R Barrack; G Prem-Veer Reddy |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-01-28 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-29 Completed Date: 2010-05-14 Revised Date: 2011-07-27 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 10472-6 Citation Subset: IM |
Affiliation:
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Vattikuti Urology Institute, Henry Ford Hospital, Detroit, Michigan 48202, USA. skim3@hfhs.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Androgen Antagonists
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pharmacology Anilides / pharmacology Blotting, Western Cell Line, Tumor Cell Proliferation / drug effects DNA Damage / drug effects Fluorescent Antibody Technique Gene Expression Regulation, Neoplastic Humans Intracellular Signaling Peptides and Proteins / genetics, metabolism Male Nitriles / pharmacology Prostatic Neoplasms / genetics, metabolism*, pathology RNA, Messenger / genetics, metabolism Receptors, Androgen / genetics, metabolism* Reverse Transcriptase Polymerase Chain Reaction Telomere / genetics, metabolism* Telomere-Binding Proteins / genetics, metabolism* Telomeric Repeat Binding Protein 1 / genetics, metabolism Telomeric Repeat Binding Protein 2 / genetics, metabolism Tosyl Compounds / pharmacology Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/AR protein, human; 0/Androgen Antagonists; 0/Anilides; 0/Intracellular Signaling Peptides and Proteins; 0/Nitriles; 0/RNA, Messenger; 0/Receptors, Androgen; 0/TERF2 protein, human; 0/TINF2 protein, human; 0/TP53BP1 protein, human; 0/Telomere-Binding Proteins; 0/Telomeric Repeat Binding Protein 1; 0/Telomeric Repeat Binding Protein 2; 0/Tosyl Compounds; 0/shelterin, human; 90357-06-5/bicalutamide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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