CCAAT/增强子结合蛋白β在前列腺增生性炎性萎缩中的表达增加：与COX-2、雄激素受体表达及局灶性慢性炎症的关系

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.

作者信息

Wang Wanzhong, Bergh Anders, Damber Jan-Erik

机构信息

Department of Urology, Lundberg Laboratory for Cancer Research, The Sahlgrenska Academy at Göteborg University, Göteborg, Sweden.

出版信息

Prostate. 2007 Aug 1;67(11):1238-46. doi: 10.1002/pros.20595.

DOI:10.1002/pros.20595

PMID:17570496

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.

摘要

背景

前列腺增生性炎性萎缩（PIA）被认为是前列腺癌的前驱病变。CCAAT/增强子结合蛋白β（C/EBPβ）是一种参与细胞增殖和分化的重要转录因子。在促炎介质诱导环氧化酶2（COX-2）的初始阶段，C/EBPβ的激活起着关键作用。在几种人类肿瘤中已报道C/EBPβ过表达。然而，C/EBPβ在人类前列腺组织中的表达及功能基本未知。

方法

对45例良性前列腺增生（BPH）样本进行C/EBPβ免疫组化染色。分析PIA病变和外观正常腺泡中C/EBPβ的表达。此外，通过双重免疫组化染色，还研究了C/EBPβ的表达及其与慢性炎症细胞密度的关系、COX-2与雄激素受体（AR）的共表达情况。

结果

在外观正常的前列腺腺泡中偶尔可观察到C/EBPβ（4.9%±6.7%，平均值±标准差），但在PIA病变中明显过表达（81.8%±16.4%）（P<0.0001）。伴有T淋巴细胞和巨噬细胞炎症的萎缩腺泡表达更高水平的C/EBPβ。此外，C/EBPβ与COX-2表达显著相关。AR下调在PIA中很常见，且也与C/EBPβ过表达有关。