Division of Pathology, School of Molecular Medical Sciences, Queen's Medical Centre, Nottingham University, Nottingham, UK.
Pancreas. 2013 Jan;42(1):135-40. doi: 10.1097/MPA.0b013e3182557ceb.
C-terminal tensin-like gene (CTEN, also known as TNS4) localizes to focal adhesions and is reported to function as an oncogene in colonic, breast, lung, and gastric cancers. Its role in pancreatic cancer is unknown and was thus investigated in this study.
C-terminal tensinlike gene expression was evaluated by immunohistochemistry in a series of pancreatic cancers. Functional activity of the CTEN was tested by manipulating cellular CTEN levels using a dual approach of gene knockdown/forced expression.
The CTEN is overexpressed in 31 (70.45%) of 44 pancreatic cancers. Functionally, changes in CTEN level did not alter cellular proliferation, but CTEN levels were positively associated with enhanced colony-forming efficiency in both Panc-1 and PSN-1 cell lines. Forced CTEN expression in Panc-1 cells stimulated cell motility, whereas knockdown of CTEN in PSN-1 inhibited cell motility in both transwell migration and wound-healing assays. Evaluation of downstream targets demonstrated that alterations in CTEN levels induced changes in focal adhesion kinase and E-cadherin, whereas integrin-linked kinase (ILK) remained unchanged.
These are the first data showing an oncogenic role for CTEN in pancreatic cancer through promotion of colony formation and cell motility. The latter may be mediated by signaling through focal adhesion kinase and inhibiting E-cadherin.
C 端张力蛋白样基因（CTEN，也称为 TNS4）定位于黏附斑，据报道在结直肠癌、乳腺癌、肺癌和胃癌中作为癌基因发挥作用。其在胰腺癌中的作用尚不清楚，因此本研究对此进行了研究。
通过免疫组织化学方法在一系列胰腺癌中评估 C 端张力蛋白样基因的表达。通过基因敲低/强制表达的双重方法来操纵细胞 CTEN 水平来测试 CTEN 的功能活性。
在 44 例胰腺癌中，31 例（70.45%）CTEN 过表达。从功能上讲，CTEN 水平的变化不会改变细胞增殖，但 CTEN 水平与 Panc-1 和 PSN-1 细胞系中增强的集落形成效率呈正相关。在 Panc-1 细胞中强制表达 CTEN 可刺激细胞迁移，而在 PSN-1 中敲低 CTEN 可在 Transwell 迁移和伤口愈合测定中抑制细胞迁移。对下游靶标的评估表明，CTEN 水平的改变诱导黏着斑激酶和 E-钙黏蛋白发生变化，而整合素连接激酶（ILK）保持不变。
这些是首次表明 CTEN 在胰腺癌中通过促进集落形成和细胞迁移发挥致癌作用的数据。后者可能通过黏着斑激酶的信号传导和抑制 E-钙黏蛋白来介导。
