肝癌中磷脂酰聚糖-3 表达与生长信号分子的关系。
Association of glypican-3 expression with growth signaling molecules in hepatocellular carcinoma.
机构信息
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
出版信息
World J Gastroenterol. 2010 Jul 28;16(28):3521-8. doi: 10.3748/wjg.v16.i28.3521.
AIM
To clarify the association of glypican-3 (GPC3) expression with Wnt and other growth signaling molecules in hepatocellular carcinoma (HCC).
METHODS
Expression of GPC3, Wnt, matrix metalloproteinases (MMPs), sulfatase (SULF)1, SULF2, and other growth signaling molecules was analyzed in HCC cell lines and tissue samples by real-time reverse transcription-polymerase chain reaction, immunoblotting, and/or immunostaining. Expression of various genes in GPC3 siRNA-transfected HCC cells was analyzed.
RESULTS
GPC3 was overexpressed in most HCCs at mRNA and protein levels and its serum levels were significantly higher in patients with HCC than in non-HCC subjects (P < 0.05). Altered expressions of various MMPs and growth signaling molecules, some of which were correlated with GPC3 expression, were observed in HCCs. Down-regulation of GPC3 expression by siRNA in GPC3-overexpressing HCC cell lines resulted in a significant decrease in expressions of MMP2, MMP14, fibroblast growth factor receptor 1, insulin-like growth factor 1 receptor. GPC3 expression was significantly correlated with nuclear/cytoplasmic localization of beta-catenin.
CONCLUSION
These results suggest that GPC3, in conjunction with MMPs and growth signaling molecules, might play an important role in the progression of HCC.
目的
阐明磷脂酰聚糖-3（GPC3）表达与肝癌（HCC）中 Wnt 和其他生长信号分子的关联。
方法
通过实时逆转录-聚合酶链反应、免疫印迹和/或免疫染色，分析 HCC 细胞系和组织样本中 GPC3、Wnt、基质金属蛋白酶（MMPs）、硫酸酯酶（SULF）1、SULF2 和其他生长信号分子的表达。分析 GPC3 siRNA 转染的 HCC 细胞中各种基因的表达。
结果
GPC3 在大多数 HCC 中在 mRNA 和蛋白水平上过度表达，其血清水平在 HCC 患者中明显高于非 HCC 患者（P < 0.05）。在 HCC 中观察到各种 MMPs 和生长信号分子的表达发生改变，其中一些与 GPC3 表达相关。在 GPC3 过表达的 HCC 细胞系中，通过 siRNA 下调 GPC3 表达导致 MMP2、MMP14、成纤维细胞生长因子受体 1、胰岛素样生长因子 1 受体的表达显著降低。GPC3 表达与β-连环蛋白的核/细胞质定位显著相关。
结论
这些结果表明，GPC3 与 MMPs 和生长信号分子一起，可能在 HCC 的进展中发挥重要作用。
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