ABSTRACT
The Wnt/ß-catenin pathway has been implicated in leukemogenesis. We found ß-catenin abnormally accumulated in both human acute T cell leukemia Jurkat cells and human erythroleukemia HEL cells. ß-Catenin can be significantly down-regulated by the Janus kinase 2 specific inhibitor AG490 in these two cells. AG490 also reduces the luciferase activity of a reporter plasmid driven by LEF/ß-catenin promoter. Similar results were observed in HEL cells infected with lentivirus containing shRNA against JAK2 gene. After treatment with 50 µM AG490 or shRNA, the mRNA expression levels of ß-catenin, APC, Axin, ß-Trcp, GSK3α, and GSK3ß were up-regulated within 12-16 h. However, only the protein levels of GSK3ß and ß-Trcp were found to have increased relative to untreated cells. Knockdown experiments revealed that the AG490-induced inhibition of ß-catenin can be attenuated by shRNA targeting ß-TrCP. Taken together; these results suggest that ß-Trcp plays a key role in the cross-talk between JAK/STAT and Wnt/ß-catenin signaling in leukemia cells.
