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Cell-lineage specificity and role of AP-1 in the prostate fibroblast androgen receptor cistrome.

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CELL LINEAGE SPECIFICITY AND ROLE OF AP1 IN THE PROSTATE FIBROBLAST ANDROGEN RECEPTOR CISTROME.docxAccepted version3.4 MBMicrosoft WordView/Open
Supplementary.docxSupporting information4.36 MBMicrosoft WordView/Open
Title: Cell-lineage specificity and role of AP-1 in the prostate fibroblast androgen receptor cistrome.
Authors: Leach, DA
Panagopoulos, V
Nash, C
Bevan, C
Thomson, AA
Selth, LA
Buchanan, G
Item Type: Journal Article
Abstract: Androgen receptor (AR) signalling in fibroblasts is important in prostate development and carcinogenesis, and is inversely related to prostate cancer mortality. However, the molecular mechanisms of AR action in fibroblasts and other non-epithelial cell types are largely unknown. The genome-wide DNA binding profile of AR in human prostate fibroblasts was identified by chromatin immunoprecipitation sequencing (ChIP-Seq), and found to be common to other fibroblast lines but disparate from AR cistromes of prostate cancer cells and tissue. Although AR binding sites specific to fibroblasts were less well conserved evolutionarily than those shared with cancer epithelia, they were likewise correlated with androgen regulation of fibroblast gene expression. Whereas FOXA1 is the key pioneer factor of AR in cancer epithelia, our data indicated that AP-1 likely plays a more important role in the AR cistrome in fibroblasts. The specificity of AP-1 and FOXA1 to binding in these cells is demonstrated using immunoblot and immunohistochemistry. Importantly, we find the fibroblast cistrome is represented in whole tissue/in vivo ChIP-seq studies at both genomic and resulting protein levels, highlighting the importance of the stroma in whole tissue -omic studies. This is the first nuclear receptor ChIP-seq study in prostatic fibroblasts, and provides novel insight into the action of fibroblast AR in prostate cancer.
Issue Date: 12-Sep-2016
Date of Acceptance: 12-Sep-2016
URI: http://hdl.handle.net/10044/1/43525
DOI: https://dx.doi.org/10.1016/j.mce.2016.09.010
ISSN: 1872-8057
Publisher: Elsevier
Start Page: 261
End Page: 272
Journal / Book Title: Molecular and Cellular Endocrinology
Volume: 439
Copyright Statement: © 2016 Elsevier Ireland Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Androgen receptor
Chromatin immunoprecipitation
Fibroblasts
Prostate cancer
Stroma
Endocrinology & Metabolism
06 Biological Sciences
11 Medical And Health Sciences
07 Agricultural And Veterinary Sciences
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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