Anoxia/reoxygenation down-regulates the expression of E-cadherin in human colon cancer cell lines

The E-cadherin-mediated cell-cell adhesiveness is a critical factor for carcinoma cell invasion and metastasis. Anoxia/reoxygenation is known to occur in cancer tissues. In this study, we investigated whether anoxia/reoxygenation induces the down-regulation of E-cadherin expression in the human colon cancer cell lines HT-29, and SW1116. Colon cancer cells were exposed to anoxia (2 h) followed by reoxygenation (4-46 h). The subsequent expression of E-cadherin on the cell surface was examined by immunocytochemistry and enzyme-linked immunosorbent assays, the total amount of E-cadherin protein was examined by Western blotting, and the E-cadherin mRNA level was examined by a real-time polymerase chain reaction assay. The expression of E-cadherin on the cell surface and the total amount of E-cadherin protein were transiently reduced after anoxia/reoxygenation. On the other hand, the E-cadherin mRNA level was not decreased during reoxygenation. Pretreatment with actinomycin D or reagents that interfere with the activation of NF-kappaB significantly attenuated the down-regulation of E-cadherin, which implicated a role for the de novo protein synthesis. These results indicate that anoxia/reoxygenation induces a transient reduction of E-cadherin expression in human colon cancer cells through NF-kappaB dependent transcriptional pathway. (C) 2004 Elsevier Ireland Ltd. All rights reserved.