Microarray Analysis Reveals Overexpression of both Integral Membrane and Cytosolic Tight Junction Genes in Endometrial Cancer Cell Lines

Abstract

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.

Comprehensive analysis of a NAD+ metabolism-derived gene signature to predict the prognosis and immune landscape in endometrial cancer

“…The results showed that HR-DDR is most frequently mutated in EC, providing an avenue to explore the role of HR-DDR deficiency targeted therapy in EC [ 48 ]. In addition, the tight junction pathway, base excision repair pathway, and oocyte meiosis pathway have been shown to be involved in the occurrence and development of EC, which is consistent with our findings [ 49–51 ].…”

A novel gene-based model for prognosis prediction of head and neck squamous cell carcinoma

“…In this study, decreased ZO-3 was found in the tumor group, suggesting that tight junction damaged by downregulation of ZO-3 might promote the cancer metastasis. However, in some other studies, upregulated ZO-3 was reported to promote cancer [ 35 , 36 ]. Future studies are needed to investigate the exact role ZO-3 played in cancer.…”