Ye Lin, Lewis-Russell Jonathan M, Sanders Andrew J, Kynaston Howard, Jiang Wen G
Metastasis and Angiogenesis Research Group, Department of Surgery, Wales College of Medicine, Heath Park, Cardiff, UK.
Urol Oncol. 2008 Mar-Apr;26(2):190-7. doi: 10.1016/j.urolonc.2007.03.027. Epub 2007 Nov 26.
Both HGF and BMP-7 have been implicated in the prostate cancer, particularly in bone metastasis. We recently demonstrated an up-regulation of BMP receptors by HGF in prostate cancer cells. Whether HGF has an effect on BMP-7 is still unknown. In the current study, we investigated the effects of HGF on the expression of BMP-7 in prostate cancer cells. Human prostate cancer cells, PC-3 and DU-145, were exposed to HGF at different concentrations for up to 24 hours. The mRNA levels of BMP7 were detected using RT-PCR and Quantitative PCR, and protein levels using Western blotting and immunocytochemistry. The levels of the BMP-7 transcripts in both PC-3 and DU-145 cells were up-regulated by the treatment with HGF in a concentration dependent and time related manner. The rise in BMP-7 mRNA was accompanied by an increase in protein levels, an effect completely blocked by the HGF antagonist, NK4. We further assessed this effect in an in vivo murine tumor model and showed that HGF up-regulated BMP-7 in prostate tumors. The antagonist of HGF, NK4 similarly blocked the induction of BMP-7 by HGF under the in vivo conditions. Taken together, HGF/SF can regulate BMP-7 expression in prostate cancer cells, both in vitro and in vivo. It may have a significant influence on the progression of prostate cancer and/or the development of bone metastasis.
肝细胞生长因子（HGF）和骨形态发生蛋白-7（BMP-7）都与前列腺癌有关，尤其是在骨转移方面。我们最近证明，在前列腺癌细胞中，HGF可上调BMP受体。HGF对BMP-7是否有影响仍不清楚。在本研究中，我们调查了HGF对前列腺癌细胞中BMP-7表达的影响。将人前列腺癌细胞PC-3和DU-145暴露于不同浓度的HGF中长达24小时。使用逆转录聚合酶链反应（RT-PCR）和定量聚合酶链反应检测BMP7的mRNA水平，使用蛋白质印迹法和免疫细胞化学检测蛋白质水平。用HGF处理后，PC-3和DU-145细胞中BMP-7转录本的水平均以浓度依赖性和时间相关性方式上调。BMP-7 mRNA的升高伴随着蛋白质水平的增加，HGF拮抗剂NK4可完全阻断这种作用。我们进一步在体内小鼠肿瘤模型中评估了这种作用，并表明HGF可上调前列腺肿瘤中BMP-7的表达。在体内条件下，HGF拮抗剂NK4同样阻断了HGF对BMP-7的诱导作用。综上所述，HGF/SF在体外和体内均可调节前列腺癌细胞中BMP-7的表达。它可能对前列腺癌的进展和/或骨转移的发展有重大影响。
