Wanzhong Wang1, Anders Bergh, Jan-Erik Damber. 1. Department of Urology, Lundberg Laboratory for Cancer Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.
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/EBPbeta) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPbeta plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBPbeta has been reported in several human tumors. Nevertheless, the C/EBPbeta expression and functions in human prostate tissue are basically unknown. METHODS: C/EBPbeta immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPbeta in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBPbeta expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated. RESULTS: C/EBPbeta 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/EBPbeta. Furthermore, C/EBPbeta correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPbeta overexpression. CONCLUSIONS: The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPbeta 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. (c) 2007 Wiley-Liss, Inc.
BACKGROUND: Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer-binding protein beta (C/EBPbeta) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBPbeta plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBPbeta has been reported in several humantumors. Nevertheless, the C/EBPbeta expression and functions in human prostate tissue are basically unknown. METHODS:C/EBPbeta immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBPbeta in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBPbeta expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated. RESULTS:C/EBPbeta 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/EBPbeta. Furthermore, C/EBPbeta correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBPbeta overexpression. CONCLUSIONS: The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBPbeta 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. (c) 2007 Wiley-Liss, Inc.
Authors: Camilla T Karlsson; Fredrik Wiklund; Henrik Grönberg; Anders Bergh; Beatrice Melin Journal: Cancers (Basel) Date: 2011-11-08 Impact factor: 6.639