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Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure

Tutkimustuotosvertaisarvioitu

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Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure. / Urbanucci, Alfonso; Marttila, Saara; Jänne, Olli A.; Visakorpi, Tapio.

julkaisussa: Prostate, Vuosikerta 72, Nro 11, 01.08.2012, s. 1223-1232.

Tutkimustuotosvertaisarvioitu

Harvard

Urbanucci, A, Marttila, S, Jänne, OA & Visakorpi, T 2012, 'Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure', Prostate, Vuosikerta. 72, Nro 11, Sivut 1223-1232. https://doi.org/10.1002/pros.22473

APA

Urbanucci, A., Marttila, S., Jänne, O. A., & Visakorpi, T. (2012). Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure. Prostate, 72(11), 1223-1232. https://doi.org/10.1002/pros.22473

Vancouver

Author

Urbanucci, Alfonso ; Marttila, Saara ; Jänne, Olli A. ; Visakorpi, Tapio. / Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure. Julkaisussa: Prostate. 2012 ; Vuosikerta 72, Nro 11. Sivut 1223-1232.

Bibtex - Lataa

@article{39be5d9843724471aeaae85eae93d0ef,
title = "Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure",
abstract = "BACKGROUND Castration-resistant prostate cancers (CRPCs) overexpress often androgen receptor (AR). Here, we investigated the effect of AR overexpression on the dynamics of AR loading and RNA polymerase II (RNA Pol II) recruitment to chromatin. Acetylation of histone 3 (AcH3) on lysines 9 and 14 (K9 and K14) was also studied. METHODS We used an LNCaP-based AR overexpression cell line model that includes a control line and two sublines, LNCaP-ARmo and LNCaP-ARhi, which overexpress AR twofold to threefold and fourfold to fivefold, respectively. Cells were exposed to 1 or 100 nM of dihydrotestosterone (DHT). Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2 (TMPRSS2) genes was performed. qRT-PCR was used to measure the levels of PSA and TMPRSS2 transcripts. RESULTS Upon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P <0.05) in AR-overexpressing cells compared to control cells. The difference in AR loading between the control and AR-overexpressing cells was abolished by a higher DHT concentration. The ratio of AcH3/H3 was increased in AR-overexpressing cells. The induction of transcription of PSA and TMPRSS2 occurred earlier in the AR-overexpressing cells. CONCLUSIONS Our findings suggest that the levels of AR potentiate the recruitment of the AR, as well as components of the basic transcription machinery, to chromatin and affect the acetylation of histones in the presence of low levels of androgens. These changes result in enhanced gene transcription of AR target genes.",
keywords = "AR, histone 3 lysine acetylation, prostatic neoplasia, PSA, RNA polymerase 2, TMPRSS2",
author = "Alfonso Urbanucci and Saara Marttila and J{\"a}nne, {Olli A.} and Tapio Visakorpi",
year = "2012",
month = "8",
day = "1",
doi = "10.1002/pros.22473",
language = "English",
volume = "72",
pages = "1223--1232",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley",
number = "11",

}

RIS (suitable for import to EndNote) - Lataa

TY - JOUR

T1 - Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure

AU - Urbanucci, Alfonso

AU - Marttila, Saara

AU - Jänne, Olli A.

AU - Visakorpi, Tapio

PY - 2012/8/1

Y1 - 2012/8/1

N2 - BACKGROUND Castration-resistant prostate cancers (CRPCs) overexpress often androgen receptor (AR). Here, we investigated the effect of AR overexpression on the dynamics of AR loading and RNA polymerase II (RNA Pol II) recruitment to chromatin. Acetylation of histone 3 (AcH3) on lysines 9 and 14 (K9 and K14) was also studied. METHODS We used an LNCaP-based AR overexpression cell line model that includes a control line and two sublines, LNCaP-ARmo and LNCaP-ARhi, which overexpress AR twofold to threefold and fourfold to fivefold, respectively. Cells were exposed to 1 or 100 nM of dihydrotestosterone (DHT). Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2 (TMPRSS2) genes was performed. qRT-PCR was used to measure the levels of PSA and TMPRSS2 transcripts. RESULTS Upon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P <0.05) in AR-overexpressing cells compared to control cells. The difference in AR loading between the control and AR-overexpressing cells was abolished by a higher DHT concentration. The ratio of AcH3/H3 was increased in AR-overexpressing cells. The induction of transcription of PSA and TMPRSS2 occurred earlier in the AR-overexpressing cells. CONCLUSIONS Our findings suggest that the levels of AR potentiate the recruitment of the AR, as well as components of the basic transcription machinery, to chromatin and affect the acetylation of histones in the presence of low levels of androgens. These changes result in enhanced gene transcription of AR target genes.

AB - BACKGROUND Castration-resistant prostate cancers (CRPCs) overexpress often androgen receptor (AR). Here, we investigated the effect of AR overexpression on the dynamics of AR loading and RNA polymerase II (RNA Pol II) recruitment to chromatin. Acetylation of histone 3 (AcH3) on lysines 9 and 14 (K9 and K14) was also studied. METHODS We used an LNCaP-based AR overexpression cell line model that includes a control line and two sublines, LNCaP-ARmo and LNCaP-ARhi, which overexpress AR twofold to threefold and fourfold to fivefold, respectively. Cells were exposed to 1 or 100 nM of dihydrotestosterone (DHT). Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2 (TMPRSS2) genes was performed. qRT-PCR was used to measure the levels of PSA and TMPRSS2 transcripts. RESULTS Upon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P <0.05) in AR-overexpressing cells compared to control cells. The difference in AR loading between the control and AR-overexpressing cells was abolished by a higher DHT concentration. The ratio of AcH3/H3 was increased in AR-overexpressing cells. The induction of transcription of PSA and TMPRSS2 occurred earlier in the AR-overexpressing cells. CONCLUSIONS Our findings suggest that the levels of AR potentiate the recruitment of the AR, as well as components of the basic transcription machinery, to chromatin and affect the acetylation of histones in the presence of low levels of androgens. These changes result in enhanced gene transcription of AR target genes.

KW - AR

KW - histone 3 lysine acetylation

KW - prostatic neoplasia

KW - PSA

KW - RNA polymerase 2

KW - TMPRSS2

UR - http://www.scopus.com/inward/record.url?scp=84862892692&partnerID=8YFLogxK

U2 - 10.1002/pros.22473

DO - 10.1002/pros.22473

M3 - Article

VL - 72

SP - 1223

EP - 1232

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 11

ER -