蛋白激酶 C 调节神经母细胞瘤细胞中蛙皮素诱导的 VEGF 快速分泌。
Protein kinase C regulates bombesin-induced rapid VEGF secretion in neuroblastoma cells.
机构信息
Department of Pediatric Surgery, 2200 Children's Way, DOT 7100, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Anticancer Res. 2012 Nov;32(11):4691-6.
BACKGROUND
Intracellular signaling responsible for gastrin-releasing peptide (GRP) receptor-mediated neovascularization is not clearly understood. We sought to determine the cellular mechanisms involved in the GRP receptor regulation of vascular endothelial growth factor (VEGF) release in neuroblastoma cells.
MATERIALS AND METHODS
BE(2)-C cells were treated with bombesin (BBS), the amphibian equivalent of GRP, Phorbol myristate acetate (PMA) a PKC agonist, or GF109293X (GFX), and analyses were performed for VEGF secretion, phosphorylated protein kinase B (AKT), extracellular signal-regulated kinases (ERK) and protein kinase D (PKD) expression.
RESULTS
BBS rapidly increased VEGF secretion at 30 min. Pre-treatment with PMA alone produced similar results; this effect was synergistic with the addition of GRP. Conversely, GFX blocked PMA-stimulated increase in VEGF secretion. Immunofluorescent staining for VEGF correlated to BBS, PMA and GFX.
CONCLUSION
PKC is critically responsible for rapid VEGF secretion by GRP receptor signaling in neuroblastoma cells. Inhibition of VEGF significantly reduced GRP-mediated cell proliferation, suggesting its crucial role in neuroblastoma tumorigenesis.
背景
目前尚不清楚负责胃泌素释放肽（GRP）受体介导的新生血管形成的细胞内信号。我们试图确定参与 GRP 受体调节神经母细胞瘤细胞中血管内皮生长因子（VEGF）释放的细胞机制。
材料和方法
用蛙皮素（BBS），GRP 的两栖等效物，佛波醇 12,13-二丁酸酯（PMA）PKC 激动剂或 GF109293X（GFX）处理 BE（2）-C 细胞，并分析 VEGF 分泌，磷酸化蛋白激酶 B（AKT），细胞外信号调节激酶（ERK）和蛋白激酶 D（PKD）的表达。
结果
BBS 在 30 分钟内迅速增加 VEGF 的分泌。单独用 PMA 预处理可产生相似的结果；这种作用与 GRP 的添加具有协同作用。相反，GFX 阻断了 PMA 刺激的 VEGF 分泌增加。VEGF 的免疫荧光染色与 BBS、PMA 和 GFX 相关。
结论
PKC 对神经母细胞瘤细胞中 GRP 受体信号介导的 VEGF 快速分泌至关重要。VEGF 的抑制显著降低了 GRP 介导的细胞增殖，表明其在神经母细胞瘤肿瘤发生中的关键作用。
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