Yin Hong, Radomska Hanna S, Tenen Daniel G, Glass Jonathan
Feist-Weiller Cancer Center and Department of Medicine, LSU Health Sciences Center, Shreveport, LA, USA.
BMC Cancer. 2006 Jun 14;6:158. doi: 10.1186/1471-2407-6-158.
C/EBPalpha is a transcription factor essential for terminal differentiation of several cell types. It has not known if C/EBPalpha protein is expressed and functions in the prostate gland.
The presence of C/EBPalpha in normal and cancerous prostate epithelium was examined by immunochemistry. Over expression of C/EBPalpha in LNCaP cells was conducted with retrovirus-mediated transduction. PSA expression was examined by RT-PCR and western blot and PSA promoter activity by luciferase reporter assay.
In normal prostate C/EBPalpha was expressed in the basal layer of the epithelium. In prostate cancer C/EBPalpha was detected at low levels throughout the cancers and in advanced prostate cancer C/EBPalpha expression was associated with decreased expression of AR and PSA. Overexpression of C/EBPalpha inhibited epigenetically PSA expression and was accompanied by the loss of expression of AR. Transient increase of C/EBPalpha inhibited the PSA promoter/enhancer activity independently of expression of AR.
In LNCaP cells C/EBPalpha over expression inhibits expression of PSA by AR -dependent and independent mechanisms and by extinguishing AR expression provides a model for hormonal independent cell growth.
C/EBPα是几种细胞类型终末分化所必需的转录因子。目前尚不清楚C/EBPα蛋白在前列腺中是否表达并发挥作用。
采用免疫化学方法检测正常和癌性前列腺上皮中C/EBPα的存在情况。通过逆转录病毒介导的转导在LNCaP细胞中过表达C/EBPα。通过RT-PCR和蛋白质印迹法检测前列腺特异性抗原（PSA）的表达，并通过荧光素酶报告基因测定法检测PSA启动子活性。
在正常前列腺中，C/EBPα在上皮的基底层表达。在前列腺癌中，整个癌组织中均检测到低水平的C/EBPα，在晚期前列腺癌中，C/EBPα表达与雄激素受体（AR）和PSA表达降低相关。C/EBPα的过表达通过表观遗传方式抑制PSA表达，并伴有AR表达缺失。C/EBPα的短暂增加独立于AR的表达抑制了PSA启动子/增强子活性。
在LNCaP细胞中，C/EBPα的过表达通过依赖AR和不依赖AR的机制抑制PSA表达，并且通过消除AR表达为激素非依赖性细胞生长提供了一个模型。
