Cuevas Maria E, Winters Chance P, Todd Maria C
Biology Department, Southwestern University, Georgetown, TX 78626.
J Cancer. 2022 Oct 31;13(14):3533-3538. doi: 10.7150/jca.75510. eCollection 2022.
Deregulation of tight junction (TJ) proteins and the associated disruption of TJ function has been demonstrated to play a role in the development of endometrial cancer. In the current study, we have shown overexpression of claudin-3 and -4 mRNA (by RT-PCR) and protein (by immunoblotting) in a panel of 9 human endometrial cancer cell lines. To further expand our understanding of the complex role of TJ deregulation in endometrial cancer, we also investigated the expression of 84 TJ and TJ-associated genes (encoding the array of proteins that function within the TJ network from the membrane to nuclear signaling pathways) by microarray analysis. Consistent with the claudin-3 and -4 RT-PCR and immunoblot findings described above, we observed overexpression of the claudin-3 and -4 genes by microarray analysis. Further, we observed overexpression of an additional three genes in 8 of the 9 endometrial cancer cell lines: OCLN (occludin), F11R (JAM-A) and TJP3 (ZO-3). OCLN and F11R encode integral membrane proteins whereas TJP3 encodes a cytosolic scaffolding protein that indirectly links membrane TJ proteins to the actin cytoskeleton and cell signaling pathways. Our data suggest that the structural disruption of TJs coupled with the downstream deregulation of signaling pathways involved in cellular proliferation and migration may contribute to the development of endometrial cancer.
紧密连接（TJ）蛋白的失调以及相关的TJ功能破坏已被证明在子宫内膜癌的发生发展中起作用。在本研究中，我们通过逆转录聚合酶链反应（RT-PCR）和免疫印迹法分别检测了9种人子宫内膜癌细胞系中claudin-3和-4的mRNA及蛋白的过表达情况。为了进一步深入了解TJ失调在子宫内膜癌中的复杂作用，我们还通过微阵列分析研究了84个TJ及TJ相关基因（编码从细胞膜到核信号通路在TJ网络中发挥作用的一系列蛋白质）的表达。与上述claudin-3和-4的RT-PCR及免疫印迹结果一致，我们通过微阵列分析观察到claudin-3和-4基因的过表达。此外，我们在9个子宫内膜癌细胞系中的8个中观察到另外三个基因的过表达：OCLN（闭合蛋白）、F11R（连接黏附分子A）和TJP3（紧密连接蛋白3）。OCLN和F11R编码整合膜蛋白，而TJP3编码一种胞质支架蛋白，它间接将膜TJ蛋白与肌动蛋白细胞骨架和细胞信号通路相连。我们的数据表明，TJ的结构破坏以及参与细胞增殖和迁移的信号通路的下游失调可能促成了子宫内膜癌的发生发展。
