Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion.

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Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion. / Battaglia, S; Maguire, O; Thorne, JL; Hornung, LB; Doig, Craig; Liu, S; Sucheston, LE; Bianchi, A; Khanim, Farhat; Gommersall, LM; Coulter, HS; Rakha, S; Giddings, I; O'Neill, Laura; Cooper, CS; McCabe, Christopher; Bunce, Christopher; Campbell, Moray.

In: Carcinogenesis, 13.05.2010.

Research output: Contribution to journalArticle

Harvard

Battaglia, S, Maguire, O, Thorne, JL, Hornung, LB, Doig, C, Liu, S, Sucheston, LE, Bianchi, A, Khanim, F, Gommersall, LM, Coulter, HS, Rakha, S, Giddings, I, O'Neill, L, Cooper, CS, McCabe, C, Bunce, C & Campbell, M 2010, 'Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion.', Carcinogenesis. https://doi.org/10.1093/carcin/bgq086

APA

Battaglia, S., Maguire, O., Thorne, JL., Hornung, LB., Doig, C., Liu, S., Sucheston, LE., Bianchi, A., Khanim, F., Gommersall, LM., Coulter, HS., Rakha, S., Giddings, I., O'Neill, L., Cooper, CS., McCabe, C., Bunce, C., & Campbell, M. (2010). Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion. Carcinogenesis. https://doi.org/10.1093/carcin/bgq086

Vancouver

Author

Battaglia, S ; Maguire, O ; Thorne, JL ; Hornung, LB ; Doig, Craig ; Liu, S ; Sucheston, LE ; Bianchi, A ; Khanim, Farhat ; Gommersall, LM ; Coulter, HS ; Rakha, S ; Giddings, I ; O'Neill, Laura ; Cooper, CS ; McCabe, Christopher ; Bunce, Christopher ; Campbell, Moray. / Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion. In: Carcinogenesis. 2010.

Bibtex

@article{506b47a51a494bf092e05154c99d4856,
title = "Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion.",
abstract = "The loss of anti-proliferative responsiveness in prostate cancer cell lines towards ligands for VDR, RARs/RXRs, and PPARalpha/gamma may entail underlying epigenetic events, as ligand insensitivity reflects significantly altered mRNA expression of co-repressors and histone modifying enzymes. Expression patterns were dependent on phases of the cell cycle and associated with repressed basal gene expression of VDR and PPARalpha/gamma target genes, for example CDKN1A (encodes p21((waf1/cip1))). Elevated NCOR1 and NCOR2/SMRT protein levels were detected in prostate cancer cell lines compared to non-malignant counterparts. Knockdown of the co-repressor NCOR1 significantly elevated basal expression of a cohort of target genes, including CDKN1A. Both chemical (HDACi) and NCOR1 knockdown targeting enhanced anti-proliferative sensitivity towards PPARalpha/gamma ligands in prostate cancer cell lines. Pursuing PPARalpha/gamma signaling, microarray approaches were undertaken to identify pathways and genes regulated uniquely by a combination of PPARalpha/gamma activation and HDAC inhibition. Again, HDACi and knockdown approaches demonstrated that elevated NCOR1 expression and activity distorted PPARalpha/gamma gene targets centered on, for example, cell cycle control, including CDKN1A and TGFBRAP1. Q-RT-PCR validation and ChIP assays both confirmed that elevated NCOR1 disrupted the ability of PPARalpha/gamma to regulate key target genes (CDKN1A and TGFBRAP1). Interrogation of these relationships in prostate cancer samples using principal component and partial correlation analyses established significant inter-dependent relationships between NCOR1-PPARalpha/gamma and representative target genes, independently of AR expression. Therefore we conclude that elevated NCOR1 distorts the actions of PPARalpha/gamma selectively and generates a potential epigenetic lesion with diagnostic and prognostic significance.",
author = "S Battaglia and O Maguire and JL Thorne and LB Hornung and Craig Doig and S Liu and LE Sucheston and A Bianchi and Farhat Khanim and LM Gommersall and HS Coulter and S Rakha and I Giddings and Laura O'Neill and CS Cooper and Christopher McCabe and Christopher Bunce and Moray Campbell",
year = "2010",
month = may,
day = "13",
doi = "10.1093/carcin/bgq086",
language = "English",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",

}

RIS

TY - JOUR

T1 - Elevated NCOR1 disrupts PPAR{alpha}/{gamma} signaling in prostate cancer and forms a targetable epigenetic lesion.

AU - Battaglia, S

AU - Maguire, O

AU - Thorne, JL

AU - Hornung, LB

AU - Doig, Craig

AU - Liu, S

AU - Sucheston, LE

AU - Bianchi, A

AU - Khanim, Farhat

AU - Gommersall, LM

AU - Coulter, HS

AU - Rakha, S

AU - Giddings, I

AU - O'Neill, Laura

AU - Cooper, CS

AU - McCabe, Christopher

AU - Bunce, Christopher

AU - Campbell, Moray

PY - 2010/5/13

Y1 - 2010/5/13

N2 - The loss of anti-proliferative responsiveness in prostate cancer cell lines towards ligands for VDR, RARs/RXRs, and PPARalpha/gamma may entail underlying epigenetic events, as ligand insensitivity reflects significantly altered mRNA expression of co-repressors and histone modifying enzymes. Expression patterns were dependent on phases of the cell cycle and associated with repressed basal gene expression of VDR and PPARalpha/gamma target genes, for example CDKN1A (encodes p21((waf1/cip1))). Elevated NCOR1 and NCOR2/SMRT protein levels were detected in prostate cancer cell lines compared to non-malignant counterparts. Knockdown of the co-repressor NCOR1 significantly elevated basal expression of a cohort of target genes, including CDKN1A. Both chemical (HDACi) and NCOR1 knockdown targeting enhanced anti-proliferative sensitivity towards PPARalpha/gamma ligands in prostate cancer cell lines. Pursuing PPARalpha/gamma signaling, microarray approaches were undertaken to identify pathways and genes regulated uniquely by a combination of PPARalpha/gamma activation and HDAC inhibition. Again, HDACi and knockdown approaches demonstrated that elevated NCOR1 expression and activity distorted PPARalpha/gamma gene targets centered on, for example, cell cycle control, including CDKN1A and TGFBRAP1. Q-RT-PCR validation and ChIP assays both confirmed that elevated NCOR1 disrupted the ability of PPARalpha/gamma to regulate key target genes (CDKN1A and TGFBRAP1). Interrogation of these relationships in prostate cancer samples using principal component and partial correlation analyses established significant inter-dependent relationships between NCOR1-PPARalpha/gamma and representative target genes, independently of AR expression. Therefore we conclude that elevated NCOR1 distorts the actions of PPARalpha/gamma selectively and generates a potential epigenetic lesion with diagnostic and prognostic significance.

AB - The loss of anti-proliferative responsiveness in prostate cancer cell lines towards ligands for VDR, RARs/RXRs, and PPARalpha/gamma may entail underlying epigenetic events, as ligand insensitivity reflects significantly altered mRNA expression of co-repressors and histone modifying enzymes. Expression patterns were dependent on phases of the cell cycle and associated with repressed basal gene expression of VDR and PPARalpha/gamma target genes, for example CDKN1A (encodes p21((waf1/cip1))). Elevated NCOR1 and NCOR2/SMRT protein levels were detected in prostate cancer cell lines compared to non-malignant counterparts. Knockdown of the co-repressor NCOR1 significantly elevated basal expression of a cohort of target genes, including CDKN1A. Both chemical (HDACi) and NCOR1 knockdown targeting enhanced anti-proliferative sensitivity towards PPARalpha/gamma ligands in prostate cancer cell lines. Pursuing PPARalpha/gamma signaling, microarray approaches were undertaken to identify pathways and genes regulated uniquely by a combination of PPARalpha/gamma activation and HDAC inhibition. Again, HDACi and knockdown approaches demonstrated that elevated NCOR1 expression and activity distorted PPARalpha/gamma gene targets centered on, for example, cell cycle control, including CDKN1A and TGFBRAP1. Q-RT-PCR validation and ChIP assays both confirmed that elevated NCOR1 disrupted the ability of PPARalpha/gamma to regulate key target genes (CDKN1A and TGFBRAP1). Interrogation of these relationships in prostate cancer samples using principal component and partial correlation analyses established significant inter-dependent relationships between NCOR1-PPARalpha/gamma and representative target genes, independently of AR expression. Therefore we conclude that elevated NCOR1 distorts the actions of PPARalpha/gamma selectively and generates a potential epigenetic lesion with diagnostic and prognostic significance.

U2 - 10.1093/carcin/bgq086

DO - 10.1093/carcin/bgq086

M3 - Article

C2 - 20466759

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

ER -