You Zongbing, Ge Dongxia, Liu Sen, Zhang Qiuyang, Borowsky Alexander D, Melamed Jonathan
Department of Structural & Cellular Biology, Department of Orthopaedic Surgery, Tulane Cancer Center, Louisiana Cancer Research Consortium, Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane Center for Aging, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Department of Pathology & Laboratory Medicine and Center for Comparative Medicine, University of California Davis, Davis, California 95616.
Int J Med Biol Front. 2012;18(8):629-644.
Interleukin-17 (IL-17A) expression is increased in prostate cancer. This study investigated the expression of IL-17A receptor C (IL-17RC) in prostatic intraepithelial neoplasia (PIN) lesions and the effects of IL-17A on prostatic epithelial cells in studies.
IL-17RC expression in human and rodent prostate tissues was detected by immunohistochemistry. Quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot analyses were used to determine mRNA and protein expression in human and mouse prostatic epithelial cell lines.
IL-17RC protein was increased in human and rodent PIN lesions, compared to the normal human and rodent prostatic epithelium. IL-17A treatment activated the Nuclear Factor-κB (NF-κB) and/or Extracellular signal-Regulated Kinase (ERK) pathways in human PIN and LNCaP cell lines as well as mouse prostate cancer cell line TRAMP-C1. IL-17A treatment did not affect cell growth of the cell lines studied. However, IL-17A induced expression of CXCL1, CXCL2, CCL2, CCL5, and IL-6 in human and mouse prostatic epithelial cell lines. When the full-length IL-17RC was over-expressed in human PIN and LNCaP cell lines, activation of NF-κB and/or ERK pathways and expression of CXCL1, CXCL2, and CCL5 chemokines were significantly enhanced upon IL-17A treatment.
These findings suggest that the prostatic epithelial cells in PIN lesions may respond to IL-17A stimuli with augmented synthesis of chemokines, due to increased IL-17RC expression.
白细胞介素-17（IL-17A）在前列腺癌中表达增加。本研究调查了前列腺上皮内瘤变（PIN）病变中IL-17A受体C（IL-17RC）的表达情况以及IL-17A在研究中对前列腺上皮细胞的影响。
通过免疫组织化学检测人和啮齿动物前列腺组织中IL-17RC的表达。采用定量实时逆转录聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析来确定人和小鼠前列腺上皮细胞系中的mRNA和蛋白质表达。
与正常人和啮齿动物前列腺上皮相比，人和啮齿动物PIN病变中IL-17RC蛋白增加。IL-17A处理激活了人PIN和LNCaP细胞系以及小鼠前列腺癌细胞系TRAMP-C1中的核因子κB（NF-κB）和/或细胞外信号调节激酶（ERK）通路。IL-17A处理不影响所研究细胞系的细胞生长。然而，IL-17A诱导人和小鼠前列腺上皮细胞系中CXCL1、CXCL2、CCL2、CCL5和IL-6的表达。当全长IL-17RC在人PIN和LNCaP细胞系中过表达时，IL-17A处理后NF-κB和/或ERK通路的激活以及CXCL1、CXCL2和CCL5趋化因子的表达显著增强。
这些发现表明，由于IL-17RC表达增加，PIN病变中的前列腺上皮细胞可能对IL-17A刺激产生反应，导致趋化因子合成增加。
