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Increased expression of CCAAT/enhancer‐binding protein beta in proliferative inflammatory atrophy of the prostate: Relation with the expression of COX‐2, the androgen receptor, and presence of focal chronic inflammation
Author(s) -
Wang Wanzhong,
Bergh Anders,
Damber JanErik
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20595
Subject(s) - prostate cancer , prostate , androgen receptor , ccaat enhancer binding proteins , downregulation and upregulation , hyperplasia , inflammation , immunohistochemistry , endocrinology , medicine , pathology , biology , transcription factor , cancer , nuclear protein , biochemistry , gene
Abstract BACKGROUND Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer‐binding protein beta (C/EBPβ) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPβ plays a crucial role during the initial stage of cyclo‐oxygenase 2 (COX‐2) induction by proinflammatory mediators. Overexpression of C/EBPβ has been reported in several human tumors. Nevertheless, the C/EBPβ expression and functions in human prostate tissue are basically unknown. METHODS C/EBPβ immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPβ in PIA lesions and normal‐appearing acini was analyzed. In addition, by using double‐IHC staining, C/EBPβ expression and the association with chronic inflammatory cell density, co‐expression of COX‐2 and androgen receptor (AR) were also investigated. RESULTS C/EBPβ was occasionally observed in normal‐appearing prostate acini (4.9% ± 6.7%, Mean ± SD) but was clearly overexpressed in PIA lesions (81.8% ± 16.4%) ( P < 0.0001). Atrophic glands with T‐lymphocyte and macrophage inflammation expressed higher level of C/EBPβ. Furthermore, C/EBPβ correlated significantly with COX‐2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPβ overexpression. CONCLUSIONS The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPβ expression in prostate epithelium, which was in turn associated with increased COX‐2 expression and AR downregulation. In combining with other molecular alteration in the epithelium of PIA, it is suggested that these cells might be a kind of intermediate cells and involved in the pathogenesis of prostate cancer. Prostate 67: 1238–1246, 2007. © 2007 Wiley‐Liss, Inc.