Department of Neurosurgery, First Affiliated Hospital of China Medical University, Shenyang 110001, PR China.
BMC Cancer. 2011 Dec 12;11:514. doi: 10.1186/1471-2407-11-514.
δ-Catenin (CTNND2), which encodes a scaffold protein in humans, has been found in a few malignancies. However, the expression pattern and contribution of δ-catenin to astrocytoma progression are unclear.
We investigated δ-catenin expression in human astrocytoma samples and its function in astrocytoma cell lines using immunohistochemistry, siRNA knockdown, transfection, MTT, transwell migration and Rac1 pulldown techniques.
δ-Catenin protein expression was detected in cytoplasm of astrocytoma cells by immunohistochemistry. Analysis showed that grade I astrocytoma (0%, 0/11) and glial cells from normal brain tissue exhibited negative staining. δ-Catenin expression was significantly higher in grade III-IV (35%, 29/84) compared to grade II astrocytoma cells (18%, 11/61); p < 0.01). In addition, CTNND2 overexpression promoted proliferation, invasion and Rac1 activity of U251 astrocytoma cells. Treatment of δ-catenin-transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. δ-Catenin knockdown in U87 glioblastoma cell decreased cell proliferation, invasion and Rac1 activity.
The results suggest that δ-catenin expression is associated with the malignant progression of astrocytoma and promotes astrocytoma cell invasion through upregulation of Rac1 activity. δ-Catenin expression levels may serve as a useful marker of the biological behavior of astrocytoma cells.
δ-连环蛋白(CTNND2)在人类中编码支架蛋白,已在几种恶性肿瘤中发现。然而,δ-连环蛋白在星形细胞瘤进展中的表达模式和作用尚不清楚。
我们通过免疫组织化学、siRNA 敲低、转染、MTT、Transwell 迁移和 Rac1 下拉技术研究了人星形细胞瘤样本中 δ-连环蛋白的表达及其在星形细胞瘤细胞系中的功能。
免疫组织化学显示 δ-连环蛋白蛋白表达在星形细胞瘤细胞质中。分析表明,Ⅰ级星形细胞瘤(0%,0/11)和正常脑组织中的神经胶质细胞呈阴性染色。与Ⅱ级星形细胞瘤细胞(18%,11/61)相比,Ⅲ-Ⅳ级星形细胞瘤(35%,29/84)中 δ-连环蛋白表达显著升高;p<0.01)。此外,CTNND2 过表达促进 U251 星形细胞瘤的增殖、侵袭和 Rac1 活性。用 Rac1 抑制剂处理 δ-连环蛋白转染细胞可降低 Rac1 活性和侵袭。U87 神经胶质瘤细胞中 δ-连环蛋白的敲低降低了细胞增殖、侵袭和 Rac1 活性。
研究结果表明,δ-连环蛋白的表达与星形细胞瘤的恶性进展有关,并通过上调 Rac1 活性促进星形细胞瘤细胞侵袭。δ-连环蛋白的表达水平可能是星形细胞瘤细胞生物学行为的一个有用标志物。