Kakehi Yoshiyuki, Segawa Takehiko, Wu Xiu-Xian, Kulkarni Prakash, Dhir Rajiv, Getzenberg Robert H
Department of Urology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan.
Prostate. 2004 Jun 1;59(4):351-6. doi: 10.1002/pros.10365.
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.
Expression profiling using 42K Affymetrix HuGeneFL 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.
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.
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.
巨噬细胞抑制细胞因子-1（MIC-1）是转化生长因子-β/骨形态发生蛋白（BMP）超家族的成员。尽管其在前列腺调节中可能发挥作用，但其生物学活性却鲜为人知。
使用42K Affymetrix HuGeneFL芯片进行表达谱分析，以比较有症状的良性前列腺增生（BPH）、无症状的组织学BPH以及来自供体的正常前列腺样本。通过RT-PCR分析前列腺上皮和基质细胞以及前列腺癌细胞LNCaP、PC-3、DU-145纯培养物中的MIC-1基因表达。通过Northern印迹分析雄激素对LNCaP细胞中MIC-1表达的影响。使用报告基因分析检测雄激素对MIC-1启动子活性的增强作用。
与正常前列腺相比，从膀胱前列腺切除标本获得的有症状BPH样本和组织学BPH中，MIC-1基因下调（分别为P < 0.005和P < 0.01）。雄激素敏感的LNCaP细胞中MIC-1的表达水平较高且受雄激素增强，而在雄激素不敏感的PC-3和DU-145细胞中表达水平较低。MIC-1基因的11 kb启动子区域被确定受雄激素激活6至12倍。
MIC-1的下调可能在BPH的发生发展中起作用。MIC-1受雄激素正向调节，但其他调节因子尚不清楚。
