p53 and the proteasome regulate androgen receptor activity

Natalya V. Guseva; Oskar W. Rokhlin; Rebecca A. Glover; Michael B. Cohen

doi:10.4161/cbt.19605

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p53 and the proteasome regulate androgen receptor activity

Journal article

Open access

Peer reviewed

p53 and the proteasome regulate androgen receptor activity

Natalya V. Guseva, Oskar W. Rokhlin, Rebecca A. Glover and Michael B. Cohen

Cancer biology & therapy, Vol.13(7), pp.553-558

05/01/2012

DOI: 10.4161/cbt.19605

PMID: 22407029

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Abstract

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 mu M 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.

Life Sciences & Biomedicine

Oncology

Science & Technology

Details

Title: Subtitle: p53 and the proteasome regulate androgen receptor activity
Creators: Natalya V. Guseva - University of Iowa
Oskar W. Rokhlin - University of Iowa
Rebecca A. Glover - University of Iowa
Michael B. Cohen - University of Iowa
Resource Type: Journal article
Publication Details: Cancer biology & therapy, Vol.13(7), pp.553-558
Publisher: Landes Bioscience
DOI: 10.4161/cbt.19605
PMID: 22407029
ISSN: 1538-4047
eISSN: 1555-8576
Number of pages: 6
Language: English
Date published: 05/01/2012
Academic Unit: Pathology; Biology
Record Identifier: 9984647059702771

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