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.

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 recrui...

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Autores principales:	Paola Barboro, Luana Borzì, Erica Repaci, Nicoletta Ferrari, Cecilia Balbi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e99c4e4891f74166bf2b6e00edc8da33
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spelling	oai:doaj.org-article:e99c4e4891f74166bf2b6e00edc8da332021-11-18T08:46:48ZAndrogen 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.1932-620310.1371/journal.pone.0079212https://doaj.org/article/e99c4e4891f74166bf2b6e00edc8da332013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24236111/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Paola BarboroLuana BorzìErica RepaciNicoletta FerrariCecilia BalbiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79212 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paola Barboro Luana Borzì Erica Repaci Nicoletta Ferrari Cecilia Balbi 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.
description	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.
format	article
author	Paola Barboro Luana Borzì Erica Repaci Nicoletta Ferrari Cecilia Balbi
author_facet	Paola Barboro Luana Borzì Erica Repaci Nicoletta Ferrari Cecilia Balbi
author_sort	Paola Barboro
title	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.
title_short	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.
title_full	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.
title_fullStr	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.
title_full_unstemmed	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.
title_sort	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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e99c4e4891f74166bf2b6e00edc8da33
work_keys_str_mv	AT paolabarboro androgenreceptoractivityisaffectedbybothnuclearmatrixlocalizationandthephosphorylationstatusoftheheterogeneousnuclearribonucleoproteinkinantiandrogentreatedlncapcells AT luanaborzi androgenreceptoractivityisaffectedbybothnuclearmatrixlocalizationandthephosphorylationstatusoftheheterogeneousnuclearribonucleoproteinkinantiandrogentreatedlncapcells AT ericarepaci androgenreceptoractivityisaffectedbybothnuclearmatrixlocalizationandthephosphorylationstatusoftheheterogeneousnuclearribonucleoproteinkinantiandrogentreatedlncapcells AT nicolettaferrari androgenreceptoractivityisaffectedbybothnuclearmatrixlocalizationandthephosphorylationstatusoftheheterogeneousnuclearribonucleoproteinkinantiandrogentreatedlncapcells AT ceciliabalbi androgenreceptoractivityisaffectedbybothnuclearmatrixlocalizationandthephosphorylationstatusoftheheterogeneousnuclearribonucleoproteinkinantiandrogentreatedlncapcells
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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.

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