| P53 and the proteasome regulate androgen receptor activity. | |
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MedLine Citation:
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PMID: 22407029 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutual regulation of expression between p53 and AR has been reported. To further investigate the role of p53 in the regulation of AR expression, an ARE-Luciferase vector was inserted into LNCaP and into LNCaP-sip53 transfectants, and AR activity was quantitatively estimated after treatment with proteasome inhibitors. LNCaP expresses a mutated form of AR. Therefore, to investigate whether p53 can modulate the expression of wild-type (wt) of AR, we transfected PC3-wtAR with a p53 vector together with ARE-Luc and showed that p53 expression decreased DHT-dependent activity of wtAR. Since proteasomes also participate in AR transcriptional activity, we investigated the role of p53 in proteasome-dependent inhibition of AR activity. More than 80% of AR activity was inhibited by 3 μM of lactacystin in LNCaP whereas no inhibition was noted in LN-sip53. We also found that lactacystin decreased AR-DNA binding 3-fold in LNCaP but no binding decrease was observed in LN-sip53. Taken together, our data show that the inhibitory effects of proteasome inhibitors are dependent on p53 status, at least in prostate cancer. Therefore, the role of p53 during treatment with proteasome inhibitors in different tumors should be further investigated. |
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Authors:
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Natalya V Guseva; Oskar W Rokhlin; Rebecca A Glover; Michael B Cohen |
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Publication Detail:
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Type: Journal Article Date: 2012-05-01 |
Journal Detail:
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Title: Cancer biology & therapy Volume: 13 ISSN: 1555-8576 ISO Abbreviation: Cancer Biol. Ther. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-07-19 Completed Date: 2012-12-14 Revised Date: 2013-02-05 |
Medline Journal Info:
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Nlm Unique ID: 101137842 Medline TA: Cancer Biol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 553-8 Citation Subset: IM |
Affiliation:
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Department of Pathology, University of Iowa, Iowa City, Iowa, USA. natalya-guseva@uiowa.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Androgen Receptor Antagonists
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pharmacology Anilides / pharmacology Antineoplastic Agents / pharmacology Cell Line, Tumor DNA-Binding Proteins / metabolism Humans Male Nitriles / pharmacology Prostatic Neoplasms / genetics, metabolism Proteasome Endopeptidase Complex / metabolism* Proteasome Inhibitors Receptors, Androgen / metabolism* Tosyl Compounds / pharmacology Tumor Suppressor Protein p53 / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Androgen Receptor Antagonists; 0/Anilides; 0/Antineoplastic Agents; 0/DNA-Binding Proteins; 0/Nitriles; 0/Proteasome Inhibitors; 0/Receptors, Androgen; 0/Tosyl Compounds; 0/Tumor Suppressor Protein p53; 90357-06-5/bicalutamide; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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