Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2
Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2
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DOI：
10.1016/j.urolonc.2016.05.027
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Munirathinam, Gnanasekar
中科院分区：
文献类型：
--
作者：
Shetty, Aditya;Dasari, Subramanyam;Munirathinam, Gnanasekar
肝细胞衍生生长因子（HDGF）是一种肝素结合生长因子，此前已被证明在多种癌症中表达。此前，HDGF 过度表达也与多种癌症的不良预后相关。然而，HDGF 在前列腺癌中的重要性尚未得到研究。在这里，我们发现 HDGF 在雄激素敏感的 LNCaP 细胞和雄激素不敏感的 DU145、22RV1 和 PC-3 细胞中过表达。强制过度表达增强了 RWPE-1 细胞的细胞活力，而 HDGF 敲低则降低了人前列腺癌细胞的细胞增殖。我们还表明，HDGF 可能作为生存相关蛋白，因为 RWPE 细胞中 HDGF 的异位过度表达上调抗凋亡蛋白 cyclin E 和 BCL-2 的表达，同时下调促凋亡蛋白 BAX 的表达。 Western blot 分析还表明 HDGF 过表达调节磷酸 AKT 和 NF-kB 的活性，这些结果与体外迁移和侵袭测定相关。接下来，我们评估了使用 HDGF 单克隆抗体和维生素 k(2) 抑制 HDGF 的治疗潜力，结果显示，用 HDGF 单克隆抗体和维生素 K-2 处理的 HDGF 过表达 RWPE 细胞中细胞增殖减少，并且 NF-kB 表达受到抑制。总的来说，我们的结果表明 HDGF 是前列腺肿瘤发生中的相关蛋白，并且可能作为前列腺癌的潜在治疗靶点。 (C) 2016 Elsevier Inc. 保留所有权利。
Hepatoma-derived growth factor (HDGF) is a heparin-binding growth factor, which has previously been shown to be expressed in a variety of cancers. HDGF overexpression has also previously been correlated with a poor prognosis in several cancers. The significance of HDGF in prostate cancer, however, has not been investigated. Here, we show that HDGF is overexpressed in both androgen-sensitive LNCaP cells and androgen-insensitive DU145, 22RV1, and PC-3 cells. Forced overexpression enhanced cell viability of RWPE-1 cells, whereas HDGF knockdown reduced cell proliferation in human prostate cancer cells. We also show that HDGF may serve as a survival related protein as ectopic overexpression of HDGF in RWPE cells up-regulated the expression of antiapoptosis proteins cyclin E and BCL-2, whereas simultaneously down-regulating proapoptotic protein BAX. Western blot analysis also showed that HDGF overexpression modulated the activity of phospho-AKT as well as NF-kB, and these results correlated with in vitro migration and invasion assays. We next assessed the therapeutic potential of HDGF inhibition with a HDGF monoclonal antibody and vitamin k(2), showing reduced cell proliferation as well as inhibition of NF-kB expression in HDGF overexpressed RWPE cells treated with a HDGF monoclonal antibody and vitamin K-2. Collectively, our results suggest that HDGF is a relevant protein in prostate oncogenesis and may serve as a potential therapeutic target in prostate cancer. (C) 2016 Elsevier Inc. All rights reserved.