title: Blockade of JAK2 activity suppressed accumulation of β-catenin in leukemic cells.
abstract: 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.
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan, Republic of China.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Liu
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Lai
authors.forename: Kai-An
authors.initials: KA
authors.lastname: Chuang
authors.forename: Yu-Jie
authors.initials: YJ
authors.lastname: Shen
authors.forename: Wensi S
authors.initials: WS
authors.lastname: Hu
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Ho
authors.forename: Yu-Bei
authors.initials: YB
authors.lastname: Chen
authors.forename: Min-Fen
authors.initials: MF
authors.lastname: Hsu
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Hsu
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Lieu
mesh_terms: 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*
chemical_list: D012333:RNA, Messenger; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; D053614:Janus Kinase 2; D000111:Acetylcysteine