Document Detail


P53 and the proteasome regulate androgen receptor activity.
MedLine Citation:
PMID:  22407029     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Natalya V Guseva; Oskar W Rokhlin; Rebecca A Glover; Michael B Cohen
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Publication Detail:
Type:  Journal Article     Date:  2012-05-01
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-07-19     Completed Date:  2012-12-14     Revised Date:  2013-02-05    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  553-8     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Iowa, Iowa City, Iowa, USA. natalya-guseva@uiowa.edu
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MeSH Terms
Descriptor/Qualifier:
Androgen Receptor Antagonists / 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:
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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