HGF/SF up-regulates the expression of bone morphogenetic protein 7 in prostate cancer cells

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. (c) 2008 Elsevier Inc. All rights reserved.