title: Silencing of Notch3 Using shRNA driven by survivin promoter inhibits growth and promotes apoptosis of human T-cell acute lymphoblastic leukemia cells.
abstract: BACKGROUND
  As a highly conserved system, the activation of the Notch pathway has been implicated in the tumorigenesis of various hematologic diseases, including leukemias, lymphomas, and multiple myeloma. The Notch3 receptor is frequently expressed in T-cell acute lymphoblastic leukemia (T-ALL).
  
  
  METHODS
  To explore its possibility as a therapeutic target for T-ALL, we investigated the effect of Notch3 silencing on Jurkat and SupT1 cells using a novel tumor-specific short hairpin RNA (shRNA) driven by survivin promoters.
  
  
  RESULTS
  We found that downregulated expression of Notch3 correlated with significant apoptosis and inhibition of proliferation.
  
  
  CONCLUSIONS
  These facts suggest that downregulating expression of Notch3 could attenuate the Notch signaling activity in T-ALL. All these results indicate that inhibition of Notch3 expression can result in potent antitumor activity in T-ALL.
authors.affiliation: Department of Clinical Laboratory and Research Center, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiang
authors.forename: Yongri
authors.initials: Y
authors.lastname: Ouyang
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Jihong
authors.initials: J
authors.lastname: Ren
authors.forename: Min
authors.initials: M
authors.lastname: Long
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Junxia
authors.initials: J
authors.lastname: Wei
authors.forename: Huizhong
authors.initials: H
authors.lastname: Zhang
authors.forename: Huishong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D000071656:Receptor, Notch3; D051880:Receptors, Notch / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C499374:NOTCH3 protein, human; D034741:RNA, Small Interfering; D000071656:Receptor, Notch3; D051880:Receptors, Notch; D000077022:Survivin