Paschke Lukasz, Rucinski Marcin, Ziolkowska Agnieszka, Zemleduch Tomasz, Malendowicz Witold, Kwias Zbigniew, Malendowicz Ludwik K
Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Swiecicki St., 60-781, Poznan, Poland,
Pathol Oncol Res. 2014 Apr;20(2):453-9. doi: 10.1007/s12253-013-9716-z. Epub 2013 Nov 23.
In search for novel molecular targets in benign prostate hyperplasia (BPH), a PCR Array based screening of 84 genes was performed. Of those, expression of ZFP91 (ZFP91 zinc finger protein) was notably upregulated. Limited data concerning the function of ZFP91 product show that it is a potential transcription factor upregulated in human acute myelogenous leukemia and most recently found to be the non-canonical NF-κB pathway regulator. In order to test this finding on a larger number of samples, prostate specimens were obtained from patients undergoing adenomectomy for BPH (n = 21), and as a control, from patients undergoing radical cystectomy for bladder cancer (prostates unchanged pathologically, n = 18). Similar studies were performed on cultured human prostate cancer cell lines: LNCaP, DU145, 22Rv1, PC-3; as well as normal prostate epithelial cells-PrEC. Methods employed included: Human Obesity PCR Array (Qiagen), QPCR and Western blotting. QPCR studies confirmed significant overexpression of ZFP91 in BPH samples. On a protein level, however, comparison between normal and BPH prostates revealed insignificant differences. As for prostate cell lines examined, all expressed ZFP91 mRNA. Western blotting analysis showed markedly higher protein levels of ZFP91 in all cancer cell lines in comparison with normal (PrEC) cells. In conclusion, the upregulated ZFP91 mRNA in BPH, not accompanied by parallel changes in ZFP91 protein levels, together with ZFP91 protein abundance in prostate cancer cell lines suggest ZFP91 involvement in these prostate diseases.
为了寻找良性前列腺增生(BPH)中的新型分子靶点,我们基于PCR阵列对84个基因进行了筛选。其中,ZFP91(ZFP91锌指蛋白)的表达显著上调。关于ZFP91产物功能的有限数据表明,它是一种在人类急性髓性白血病中上调的潜在转录因子,最近还被发现是非经典NF-κB途径的调节因子。为了在更多样本上验证这一发现,我们从接受BPH腺瘤切除术的患者(n = 21)中获取前列腺标本,并作为对照,从接受膀胱癌根治性膀胱切除术的患者(前列腺病理未改变,n = 18)中获取标本。我们还对培养的人前列腺癌细胞系:LNCaP、DU145、22Rv1、PC-3;以及正常前列腺上皮细胞-PrEC进行了类似研究。采用的方法包括:人类肥胖PCR阵列(Qiagen)、定量PCR(QPCR)和蛋白质免疫印迹法。QPCR研究证实BPH样本中ZFP91有显著过表达。然而,在蛋白质水平上,正常前列腺和BPH前列腺之间的比较显示差异不显著。至于所检测的前列腺细胞系,均表达ZFP91 mRNA。蛋白质免疫印迹分析显示,与正常(PrEC)细胞相比,所有癌细胞系中ZFP91的蛋白质水平明显更高。总之,BPH中ZFP91 mRNA上调,但ZFP91蛋白质水平没有相应变化,以及前列腺癌细胞系中ZFP91蛋白质丰度较高,提示ZFP91参与了这些前列腺疾病。