Brubaker K D, Corey E, Brown L G, Vessella R L
Department of Urology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
J Cell Biochem. 2004 Jan 1;91(1):151-60. doi: 10.1002/jcb.10679.
Prostate cancer is the most commonly diagnosed malignancy in men and is often associated with bone metastases. Prostate cancer bone lesions can be lytic or schlerotic, with the latter predominating. Bone morphogenetic proteins (BMPs) are a family of growth factors, which may play a role in the formation of prostate cancer osteoblastic bone metastases. This study evaluated the effects of BMPs on prostate cancer cell lines. We observed growth inhibitory effects of BMP-2 and -4 on LNCaP, while PC-3 was unaffected. Flow cytometric analysis determined that LNCaP cell growth was arrested in G(1) after bone morphogenetic protein-2 treatment. Treatment of LNCaP and PC-3 with BMP-2 and -4 activated downstream signaling pathways involving SMAD-1, up-regulation of p21(CIP1/WAF1) and changes in retinoblastoma (Rb) phosphorylation. Interestingly, bone morphogenetic protein-2 treatment stimulated a 2.7-fold increase in osteoprotegerin (OPG), a molecule, which inhibits osteoclastogenesis, production in PC-3.
前列腺癌是男性中最常被诊断出的恶性肿瘤，且常与骨转移相关。前列腺癌骨病变可以是溶骨性的或硬化性的，以后者为主。骨形态发生蛋白（BMPs）是一类生长因子，可能在前列腺癌成骨性骨转移的形成中起作用。本研究评估了BMPs对前列腺癌细胞系的影响。我们观察到BMP-2和-4对LNCaP有生长抑制作用，而PC-3不受影响。流式细胞术分析确定，骨形态发生蛋白-2处理后，LNCaP细胞生长停滞在G(1)期。用BMP-2和-4处理LNCaP和PC-3激活了涉及SMAD-1的下游信号通路，上调了p21(CIP1/WAF1)并改变了视网膜母细胞瘤（Rb）的磷酸化。有趣的是，骨形态发生蛋白-2处理刺激了骨保护素（OPG）在PC-3中的产生增加2.7倍，OPG是一种抑制破骨细胞生成的分子。
