Bone morphogenetic protein signaling in prostate cancer cell lines
Bone morphogenetic protein signaling in prostate cancer cell lines
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DOI：
10.1002/jcb.10679
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发表时间：
2004-01-01
影响因子：
4
通讯作者：
Vessella, RL
中科院分区：
文献类型：
--
作者：
Brubaker, KD;Corey, E;Vessella, RL
前列腺癌是男性最常见的恶性肿瘤，通常与骨转移有关。前列腺癌的骨病变可以是溶解性的或硬化性的，后者占主导地位。骨形态发生蛋白（BMPs）是一个生长因子家族，可能在前列腺癌成骨细胞骨转移的形成中发挥作用。本研究评价骨形成蛋白对前列腺癌细胞系的作用。我们观察到BMP-2和-4对LNCaP的生长抑制作用，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细胞的生长被阻滞在G（1）。用BMP-2和BMP-4处理LNCaP和PC-3激活下游信号通路，包括SMAD-1、p21（CIP 1/WAF 1）上调和视网膜母细胞瘤（Rb）磷酸化的变化。有趣的是，骨形态发生蛋白-2治疗刺激了PC-3中骨保护素（OPG）的2.7倍增加，OPG是一种抑制破骨细胞生成的分子。(C)2003 Wiley-Liss，Inc.
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. (C) 2003 Wiley-Liss, Inc.