title: Downregulation of γ-catenin inhibits CML cell growth and potentiates             the response of CML cells to imatinib through β-catenin inhibition.
abstract: γ-catenin plays different roles in different types of tumors, and its role             in chronic myeloid leukemia (CML) cells has yet to be identified. In our study,             two CML cell lines (K562, KU812) had higher γ-catenin expression levels compared             to five types of BCR-ABL-negative leukemia cells. Knockdown of the expression             of BCR-ABL resulted in downregulation of γ-catenin. Furthermore, downregulation             of γ-catenin by siRNA inhibited the proliferation and colony formation of CML             cells and the expression of the c-Myc and cyclin D1 genes; downregulation of γ-catenin             also potentiated the effects of imatinib (inhibiting CML cell proliferation and             inducing apoptosis) and suppressed the anti-apoptotic genes Bcl-xL and survivin.             We also showed that downregulation of γ-catenin suppressed the phosphorylation             of STAT5, promoted the phosphorylation of β-catenin and reduced the translocation             of β-catenin into the nucleus, although there were no effects on the total level             of β-catenin expression in the whole cells. Furthermore, downregulation of γ-catenin             was found to promote glycogen synthase kinase-3β (GSK3β) and inhibit its phosphorylation.             Collectively, our results suggest that γ-catenin is an oncogene protein in CML             that can be regulated by BCR-ABL and that suppression of γ-catenin inhibits CML             cell growth and potentiates the effects of imatinib on CML cells through inhibition             of the activation of STAT5 and suppression of β-catenin by activating GSK3β.
authors.affiliation: Department of Clinical Hematology, The Third Military Medical                     University, Chongqing 400038, P.R. China.
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Niu
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Zhen-Dong
authors.initials: ZD
authors.lastname: Yang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhang
authors.forename: Wei-Ru
authors.initials: WR
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.forename: Wei-Ke
authors.initials: WK
authors.lastname: Si
mesh_terms: D021581:Active Transport, Cell Nucleus; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D050799:STAT5 Transcription Factor / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*; D051185:gamma Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D050799:STAT5 Transcription Factor; D051176:beta Catenin; D051185:gamma Catenin; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3