Please use this identifier to cite or link to this item:
Title: Inflammation-mediated abrogation of androgen signaling: An in vitro model of prostate cell inflammation
Authors: Debeleç Bütüner, Bilge
Alapınar, Cansu
Varışlı, Lokman
Erbaykent Tepedelen, Burcu
Hamid, Syed Muhammad
Gönen Korkmaz, Ceren
Korkmaz, Kemal Sami
Keywords: Androgen
DNA damage
Loss of p53
Prostate cancer
Issue Date: Feb-2014
Publisher: John Wiley and Sons Inc.
Source: Debeleç Bütüner, B., Alapınar, C., Varışlı, L., Erbaykent Tepedelen, B., Hamid, S. M., Gönen Korkmaz, C., and Korkmaz, K.S. (2014). Inflammation-mediated abrogation of androgen signaling: An in vitro model of prostate cell inflammation. Molecular Carcinogenesis, 53(29), 85-97. doi:10.1002/mc.21948
Abstract: As a link between inflammation and cancer has been reported in many studies, we established an in vitro model of prostatic inflammation to investigate the loss of androgen receptor (AR)-mediated signaling in androgen responsive prostate cell lines. First, the U937 monocyte cell line was differentiated into macrophages using phorbol acetate (PMA), and cells were induced with lipopolysaccharide (LPS) for cytokine secretion. Next, the cytokine levels (TNFα, IL-6, and IL1β) in conditioned media (CM) were analyzed. Prostate cells were then fed with CM containing varying concentrations of TNFα, and IkB degradation, nuclear factor kappa B (NFκB) translocation and transactivation, and the expression of matrix metalloproteinase-8 (MMP8) and matrix metalloproteinase-9 (MMP9) were then assessed. As a result of CM treatment, ubiquitin-mediated AR degradation, which was restored using anti-TNFα antibody neutralization, led to both a decrease in KLK4, PSA, and NKX3.1 expression levels and the upregulation of GPX2. In addition to the loss of AR, acute and chronic CM exposure resulted in p53 degradation and consequent p21 downregulation, which was also restored by either androgen administration or ectopic NKX3.1 expression via the stabilization of MDM2 levels in LNCaP cells. Additionally, CM treatment enhanced H2AX(S139) phosphorylation (a hallmark of DNA damage) and genetic heterogeneity in the absence of androgens in prostate cells without activating mitochondrial apoptosis. Thus, the data suggest that inflammatory cytokine exposure results in the loss of AR and p53 signaling in prostate cells and facilitates genetic heterogeneity via ROS accumulation to promote prostate carcinogenesis.
ISSN: 0899-1987
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

Files in This Item:
File Description SizeFormat 
5572.pdfMakale3.92 MBAdobe PDFThumbnail
Show full item record

CORE Recommender


checked on Mar 27, 2023


checked on Mar 25, 2023

Page view(s)

checked on Mar 27, 2023


checked on Mar 27, 2023

Google ScholarTM



Items in GCRIS Repository are protected by copyright, with all rights reserved, unless otherwise indicated.