NDLI: Androgen Receptor Activity Is Affected by Both Nuclear Matrix Localization and the Phosphorylation Status of the Heterogeneous Nuclear Ribonucleoprotein K in Anti-Androgen-Treated LNCaP Cells

Content Provider	PubMed Central
Author	Paola, Barboro Borzì, Luana Repaci, Erica Ferrari, Nicoletta Balbi, Cecilia
Editor	Lobaccaro, Jean-marc A.
Copyright Year	2013
Abstract	The androgen receptor (AR) plays a central role in the development and progression of prostate cancer (PCa) and anti-androgen therapy is a standard treatment. Unfortunately, after a few years, the majority of patients progress, developing androgen-independent PCa. AR-driven gene transcription recruits a large number of co-activator/co-repressor complexes; among these, the heterogeneous nuclear ribonucleoprotein K (hnRNP K) directly interacts with and regulates the AR translational apparatus. Here we examined AR and hnRNP K expression in response to the treatment of LNCaP cells with anti-androgen cyproterone acetate (CPA) or bicalutamide (BIC). AR and hnRNP K modulation and compartmentalization were studied by Western blot and confocal microscopy. Phosphate-affinity gel electrophoresis was employed to examine how anti-androgens modified hnRNP K phosphorylation. 10−6 M CPA significantly stimulated LNCaP proliferation, whereas for 10−4 M CPA or 10−5 M BIC an antagonistic effect was observed. After anti-androgen treatment, AR expression was remarkably down-regulated within both the cytoplasm and the nucleus; however, when CPA had an agonist activity, the AR associated with the nuclear matrix (NM) increased approximately 2.5 times. This increase was synchronous with a higher PSA expression, indicating that the NM-associated AR represents the active complex. After BIC treatment, hnRNP K expression was significantly lower in the NM, the protein was hypophosphorylated and the co-localization of AR and hnRNP K decreased. In contrast, CPA as an agonist caused hnRNP K hyperphosphorylation and an increase in the co-localization of two proteins. These findings demonstrate that, in vitro, there is a strong relationship between NM-associated AR and both cell viability and PSA levels, indicating that AR transcriptional activity is critically dependent on its subnuclear localization. Moreover, the agonistic/antagonistic activity of anti-androgens is associated with modifications in hnRNP K phosphorylation, indicating an involvement of this protein in the AR transcriptional activity and likely in the onset of the androgen-independent phenotype.
Related Links	http://dx.doi.org/10.1371/journal.pone.0079212
Starting Page	79212
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	11
Volume Number	8
Language	English
Publisher	Public Library of Science
Publisher Date	2013-11-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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