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

• BACKGROUND Proliferative inflammatory atrophy (PIA) in the prostate has been proposed to be a precursor to prostate cancer. CCAAT/enhancer-binding protein beta (C/EBP) is an important transcription factor involved in cellular proliferation and differentiation. Activation of C/EBP plays a crucial role during the initial stage of cyclo-oxygenase 2 (COX-2) induction by proinflammatory mediators. Overexpression of C/EBP has been reported in several human tumors. Nevertheless, the C/EBP expression and functions in human prostate tissue are basically unknown. METHODS C/EBP immunohistochemical staining was performed on 45 benign prostate hyperplasia (BPH) samples. The expression of C/EBP in PIA lesions and normal-appearing acini was analyzed. In addition, by using double-IHC staining, C/EBP expression and the association with chronic inflammatory cell density, co-expression of COX-2 and androgen receptor (AR) were also investigated. RESULTS C/EBP 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/EBP. Furthermore, C/EBP correlated significantly with COX-2 expression. Downregulation of the AR was common in PIA and was also related to the C/EBP overexpression. CONCLUSIONS The data demonstrated that chronic inflammation appeared to play roles in the induction of C/EBP 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Urology and Nephrology (hsv//eng)

Nyckelord

proliferative inflammatory atrophy • chronic inflammation • CCAAT/enhancer-binding protein beta • COX-2 • androgen receptor

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