Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer.
Expression of RAC 3, a steroid hormone receptor co-activator in prostate cancer.
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DOI：
10.1054/bjoc.2001.2179
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发表时间：
2001-12-14
影响因子：
8.8
通讯作者：
Robson CN
中科院分区：
文献类型：
--
作者：
Gnanapragasam VJ;Leung HY;Pulimood AS;Neal DE;Robson CN
Rac 3是p160共激活剂家族中的一员，已知能增强许多类固醇受体的转录活性。由于共激活剂也被认为可以增强雄激素受体(AR)的活性，我们研究了RAC3在前列腺癌中的作用。在前列腺癌细胞系中，我们发现Rac3蛋白在AR阳性的LNCaP细胞中表达最高，在AR阴性的PC 3细胞中中等表达，在AR阴性的DU 145细胞中低水平表达。免疫沉淀研究表明，内源性Rac3在体内与AR相互作用，转染实验证实Rac3增强了AR的转录活性。在临床前列腺癌组织中，Rac3mRNA表达较强，免疫组织化学显示Rac3mRNA在良性前列腺组织中主要在腔上皮细胞中表达，而在原发恶性上皮中表达更均匀。在37例患者中，Rac 3的表达水平与肿瘤分级(P=0.0 1)和疾病分期(P=0.0 3)显著相关，而与血清PSA水平无关。此外，Rac3的中等或高表达与较差的疾病特异性生存相关(P=0.03)。结论：Rac3是前列腺癌AR的重要辅助激活因子，可能在前列腺癌的发生发展中起重要作用。©2001癌症研究活动http://www.bjcancer.com
RAC 3, one of the p160 family of co-activators is known to enhance the transcriptional activity of a number of steroid receptors. As co-activators are also known to enhance androgen receptor (AR) activity, we investigated the role of RAC 3 in the context of prostate cancer. In prostate cancer cell lines, we found variable levels of the RAC 3 protein with highest expression seen in AR-positive LNCaP cells, moderate expression in AR-negative PC 3 cells and low-level expression in AR-negative DU 145 cells. Immuno-precipitation studies showed that endogenous RAC 3 interacted with the AR in vivo and transfection assays confirmed that RAC 3 enhanced AR transcriptional activity. In clinical prostate tissue, we found strong RAC 3 mRNA expression and immuno-histochemistry demonstrated that in benign tissue, the protein was expressed predominantly in luminal cells, while in primary malignant epithelium it was more homogeneously expressed. In a series of 37 patients, the levels of RAC 3 expression correlated significantly with tumour grade (P = 0.01) and stage of disease (P = 0.03) but not with serum PSA levels. In addition moderate or high RAC 3 expression was associated with poorer disease-specific survival (P = 0.03). We conclude that RAC 3 is an important co-activator of the AR in the prostate and may have an important role in the progression of prostate cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com
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