PSCA过表达与前列腺癌恶性生长和进展密切相关。本课题组的前期研究发现：RNA干扰沉默PSCA基因的人前列腺癌PC-3M细胞生长及体外侵袭能力显著降低，同时伴有IL-6分泌水平的显著下降。已知IL-6表达主要由IL-6基因启动子在转录水平调控，而NF-κB是其关键的转录活化因子。RAS/RAC-1/p38/ERK-1/2信号转导通路作为上游效应基因在NF-κB的活化过程中具有重要作用。据此我们首次提出：PSCA表达可能通过以上信号流激活NF-κB，诱导前列腺癌细胞自分泌IL-6。本项目拟以体内、外高表达PSCA和沉默PSCA基因的人前列腺癌模型为平台，研究PSCA基因表达对癌细胞自分泌IL-6能力、RAS/RAC-1/p38/ERK-1/2通路及其下游NF-κB和IL-6基因启动子转录活性的影响，阐明PSCA对人前列腺癌细胞自分泌IL-6的调控作用及其机制，为前列腺癌的治疗提供新的切入点。

The overexpression of prostate stem cell antigen (PSCA) was associated with the malignant proliferation and progression in human prostate cancer. Our prior data showed that human prostate cancer PC-3M cells had significantly reduced growth and invasive ability when PSCA gene was targetedly silenced by RNA interference, and that this procession was followed by the significantly lowered interleukin-6 (IL-6) levels autocrined by cancer cells. It is well-known that transcriptional control at the promoter of IL-6 gene is a major component regulating IL-6 expression levels, in which NF-κB is a key transcriptional activator. RAS/RAC-1/p38/ERK-1/2 signal transduction pathway as upstream effectors has an important role in the activation of NF-κB. Thus, we infer that PSCA expression may induce autocrine IL-6 in prostate cancer cells by activating NF-κB through the RAS/RAC-1/p38/ERK-1/2 pathway. On the platform of over-expressed and silenced PSCA human prostate cancer models in vitro and in vivo established by our previous work, the present study is to investigate the effects of PSCA expression on autocrine IL-6, RAS/RAC-1/p38/ERK-1/2 and its downstream NF-κB, and transcriptional activity of IL-6 gene promoter in prostate cancer cells, further to elucidate the mechanisms of PSCA gene regulating autocrine IL-6 in prostate cancer cells. The goal of this study is to provide the novel strategies for treatment of human prostate cancer.