Albasri Abdulkader, Seth Rashmi, Jackson Darryl, Benhasouna Ahmed, Crook Simon, Nateri Abdolrahman S, Chapman Roger, Ilyas Mohammad
Division of Pathology, Nottingham University, Nottingham NG7 2UH, UK.
J Pathol. 2009 May;218(1):57-65. doi: 10.1002/path.2508.
The Tensin gene family encodes proteins thought to modulate integrin function. C-terminal Tensin-like (CTEN) is a member of the Tensin gene family which lacks the N-terminus actin-binding domain. Cten is reported to have both oncogenic and tumour-suppressor functions. We investigated the role that Cten may play in colorectal cancer (CRC). By quantitative RT-PCR CTEN is up-regulated (i.e. > two-fold increase) in 62% of cell lines and 69% of tumours compared with normal mucosa, consistent with CTEN being a possible oncogene. Stable transfection of HCT116 and SW480 (CRC cell lines with low endogenous Cten expression) with a Cten expression vector gave identical results in both cell lines. Forced Cten expression did not cause change in cell numbers, although it did confer resistance to staurosporine-induced apoptosis (p < 0.005). Cten also induced epithelial-mesenchymal transition (EMT) in tumour cells accompanied by a significant increase in both cell migration (transwell migration and cell wounding assays, p < 0.001 and p < 0.05, respectively) and cell invasion (invasion through Matrigel, p < 0.001). Given the observed EMT, we investigated the levels of E-cadherin. Cten induction was associated with a reduction in E-cadherin protein expression but not levels of E-cadherin mRNA. These data suggest that CTEN is an oncogene in CRC which stimulates EMT, cell migration and invasion and may therefore have a role in tumour invasion/spread. Furthermore, Cten induction is associated with post-transcriptional repression of E-cadherin.
张力蛋白基因家族编码的蛋白质被认为可调节整合素功能。C端类张力蛋白（CTEN）是张力蛋白基因家族的成员，它缺乏N端肌动蛋白结合结构域。据报道，Cten具有致癌和肿瘤抑制功能。我们研究了Cten在结直肠癌（CRC）中可能发挥的作用。通过定量逆转录聚合酶链反应（RT-PCR），与正常黏膜相比，62%的细胞系和69%的肿瘤中CTEN上调（即增加两倍以上），这与CTEN可能是一种癌基因一致。用Cten表达载体稳定转染HCT116和SW480（内源性Cten表达低的CRC细胞系）在这两种细胞系中得到了相同的结果。尽管强制表达Cten确实赋予了对星形孢菌素诱导的细胞凋亡的抗性（p<0.005），但并未导致细胞数量的变化。Cten还诱导肿瘤细胞发生上皮-间质转化（EMT），同时细胞迁移（transwell迁移和细胞划痕试验，分别为p<0.001和p<0.05）和细胞侵袭（通过基质胶侵袭，p<0.001）均显著增加。鉴于观察到的EMT，我们研究了E-钙黏蛋白的水平。Cten诱导与E-钙黏蛋白蛋白表达降低有关，但与E-钙黏蛋白mRNA水平无关。这些数据表明，CTEN是CRC中的一种癌基因，可刺激EMT、细胞迁移和侵袭，因此可能在肿瘤侵袭/扩散中起作用。此外，Cten诱导与E-钙黏蛋白的转录后抑制有关。
