Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines

Paola Barboro, Erica Repaci, Nicoletta Ferrari, Alessandra Rubagotti, Francesco Boccardo, Cecilia Balbi

Research output: Contribution to journalArticle

Abstract

BACKGROUND Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma. METHODS NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation. RESULTS Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment. CONCLUSION This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor.

Original languageEnglish
Pages (from-to)1466-1479
Number of pages14
JournalProstate
Volume71
Issue number13
DOIs
Publication statusPublished - Sep 15 2011

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Heterogeneous-Nuclear Ribonucleoprotein K
Nuclear Matrix-Associated Proteins
Androgen Receptors
Prostatic Neoplasms
Cell Line
Prostate
Carcinoma
Gynecomastia
Nuclear Matrix
Electrophoresis, Gel, Two-Dimensional
Drug Combinations
Tamoxifen
Immunoprecipitation
Confocal Microscopy
Proteomics
Appointments and Schedules
Proteins
Western Blotting
Hormones
afimoxifene

Keywords

  • 4-hydroxy-tamoxifen
  • androgen receptor
  • bicalutamide
  • confocal laser scanning microscopy
  • heterogeneous nuclear ribonucleoprotein K
  • nuclear matrix
  • prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

@article{55551be68c104f9599c0a54deb9fe0c4,
title = "Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines",
abstract = "BACKGROUND Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50{\%} of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma. METHODS NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation. RESULTS Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment. CONCLUSION This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor.",
keywords = "4-hydroxy-tamoxifen, androgen receptor, bicalutamide, confocal laser scanning microscopy, heterogeneous nuclear ribonucleoprotein K, nuclear matrix, prostate cancer",
author = "Paola Barboro and Erica Repaci and Nicoletta Ferrari and Alessandra Rubagotti and Francesco Boccardo and Cecilia Balbi",
year = "2011",
month = "9",
day = "15",
doi = "10.1002/pros.21366",
language = "English",
volume = "71",
pages = "1466--1479",
journal = "Prostate",
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number = "13",

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TY - JOUR

T1 - Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines

AU - Barboro, Paola

AU - Repaci, Erica

AU - Ferrari, Nicoletta

AU - Rubagotti, Alessandra

AU - Boccardo, Francesco

AU - Balbi, Cecilia

PY - 2011/9/15

Y1 - 2011/9/15

N2 - BACKGROUND Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma. METHODS NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation. RESULTS Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment. CONCLUSION This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor.

AB - BACKGROUND Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma. METHODS NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation. RESULTS Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment. CONCLUSION This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor.

KW - 4-hydroxy-tamoxifen

KW - androgen receptor

KW - bicalutamide

KW - confocal laser scanning microscopy

KW - heterogeneous nuclear ribonucleoprotein K

KW - nuclear matrix

KW - prostate cancer

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U2 - 10.1002/pros.21366

DO - 10.1002/pros.21366

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JO - Prostate

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SN - 0270-4137

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