Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia
Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia
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DOI：
10.1002/pros.10365
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发表时间：
2004-06-01
期刊：
影响因子：
2.8
通讯作者：
Getzenberg, RH
中科院分区：
文献类型：
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作者：
Kakehi, Y;Segawa, T;Getzenberg, RH
背景巨噬细胞抑制性细胞因子-1（macrophage inhibitory cytokine-1，MIC-1）是转化生长因子-β/骨形态发生蛋白（transforming growth factor-beta/bone morphogenetic protein，BMP）超家族成员。尽管其在前列腺调节中的潜在作用，但对其生物活性知之甚少。使用42 K Affyphase HuGeneFL（R）阵列进行表达谱分析，以比较有症状的良性前列腺增生（BPH）、无症状的组织学BPH和来自供体的正常前列腺样品。通过RT-PCR分析MIC-1基因在前列腺上皮细胞和基质细胞以及前列腺癌细胞LNCaP、PC-3、DU-145的纯培养物中的表达。北方印迹法分析雄激素对LNCaP细胞MIC-1表达的影响。增强启动子活性的MIC-1雄激素进行了检查使用报告分析。与正常前列腺组织相比，有症状的BPH组织和膀胱癌切除术后组织中MIC-1基因表达下调（分别为P < 0.005和P < 0.01）。MIC-1在雄激素敏感的LNCaP细胞中的表达水平高，并被雄激素增强，而在雄激素不敏感的PC-3和DU-145细胞中的表达水平低。MIC-1基因启动子区11 kb，可被雄激素激活6 ~ 12倍。MIC-1的下调可能在BPH的发生发展中起一定作用。MIC-1受雄激素的正调控，但其他调控因素尚不清楚。(C)2003Wiley-Liss，Inc.
BACKGROUND. Macrophage inhibitory cytokine-1 (MIC-1) is a member of transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily. Despite its potential role in prostatic regulation, little is known about its biological activity.METHODS. Expression profiling using 42K Affymetrix HuGeneFL(R), array was conducted to compare symptomatic benign prostatatic hyperplasia (BPH), histological BPH without symptoms, and normal prostate samples from donors. MIC-1 gene expression was analyzed by RT-PCR in pure culture of prostate epithelial and stromal cells, and prostate cancer cells, LNCaP, PC-3, DU-145. Influence of androgens on MIC-1 expression in LNCaP cells was analyzed by Northern blot. Enhancement of promoter activity of MIC-1 by androgens was examined using reporter assays.RESULTS. In contrast to normal prostates, MIC-1 gene was down-regulated in BPH samples with symptoms and histological BPH obtained from cystoprostatectomy specimens (P < 0.005 and P < 0.01, respectively). Expression level of MIC-1 in androgen-sensitive LNCaP cells was high and enhanced by androgens, whereas in the androgen-insensitive PC-3 and DU-145 cells the expression level was low. An 11 kb promoter region of MIC-1 gene was identified to be 6- to 12-fold activated by androgens.CONCLUSIONS. Down-regulation of MIC-1 may play a role in the development of BPH. MIC-1 is positively regulated by androgens, but other regulatory factors remain unclear. (C) 2003Wiley-Liss, Inc.