Redox regulation of annexin 2 and its implications for oxidative stress-induced renal carcinogenesis and metastasis.

摘要: Ferric nitrilotriacetate (Fe-NTA) induces oxidative renal damage leading to a high incidence of cell carcinoma (RCC) in rats. Differential display analysis such RCCs revealed elevated expression annexin 2 (Anx2), substrate for kinases and receptor tissue-type plasminogen activator plasminogen. We conducted this study clarify the significance Anx2 Fenton reaction-based carcinogenesis. Messenger RNA protein levels were increased time-dependently rat kidney after Fe-NTA administration as well LLC-PK1 cells exposure H2O2. The latter was inhibited by pretreatment with N-acetylcysteine, pyrrolidine dithiocarbamate or catalase. Immunohistochemistry negligible staining normal proximal tubules, but strong regenerating karyomegalic RCCs. Metastasizing showed higher levels. phosphorylated at serine tyrosine residues these coimmunoprecipitated actin. Overexpression induced proliferation rate cells. In contrast, decrease apoptosis observed antisense treatment lines established from Fe-NTA-induced These results suggest that is regulated redox status, persistent operation adaptive mechanism plays role metastasis stress-induced cancer.