Blockade of JAK2 activity suppressed accumulation of β-catenin in leukemic cells.
The Wnt/β-catenin pathway has been implicated in leukemogenesis. We found β-catenin abnormally accumulated in both human acute T cell leukemia Jurkat cells and human erythroleukemia HEL cells. β-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/β-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 β-catenin, APC, Axin, β-Trcp, GSK3α, and GSK3β were up-regulated within 12-16 h. However, only the protein levels of GSK3β and β-Trcp were found to have increased relative to untreated cells. Knockdown experiments revealed that the AG490-induced inhibition of β-catenin can be attenuated by shRNA targeting β-TrCP. Taken together; these results suggest that β-Trcp plays a key role in the cross-talk between JAK/STAT and Wnt/β-catenin signaling in leukemia cells.
Liu
Ya-Chen
YC
Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Lai
Wei-Chih
WC
Chuang
Kai-An
KA
Shen
Yu-Jie
YJ
Hu
Wensi S
WS
Ho
Cheng-Han
CH
Chen
Yu-Bei
YB
Hsu
Min-Fen
MF
Hsu
Hui-Chi
HC
Lieu
Chien-Hui
CH
D000111:Acetylcysteine / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology; D015458:Leukemia, T-Cell / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics*; D044844:beta-Transducin Repeat-Containing Proteins / Q000502:physiology*
D012333:RNA, Messenger; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; D053614:Janus Kinase 2; D000111:Acetylcysteine