title: Down-regulation of wt1 expression in leukemia cell lines as part of apoptotic effect in arsenic treatment using two compounds.
abstract: Arsenic trioxide (As2O3) induces remission in patients with acute promyelocytic leukemia (APL). To better understand molecular mechanisms of arsenic actions, this study investigated the effect of two different arsenic compounds on gene expression of apoptosis and cellular proliferation related genes. The Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. HL-60 and K562 were treated with arsenic trioxide (As2O3) and sodium arsenite (NaAsO2) at concentrations between 0 - 10 microM for up to 48 h. The induction of apoptosis was accompanied by down-regulation of hTERT and wt1 mRNA and protein expression but up-regulation of par-4. Low concentrations of 0.1 microM arsenic induced expression of the anti-apoptotic bcl-2 gene in both cell lines HL-60 and K562. There were no major differences encountered between compounds. After arsenic treatment of the leukemia cell lines HL-60 and K562 the up-regulation of par-4 may contribute to the induction of apoptosis rather than down-regulation of bcl-2. The therapeutic effect of arsenic is the induction of apoptosis by modulating the gene expression profile of pro- and anti-apoptotic genes including the wt1 gene.
authors.affiliation: Department of Internal Medicine II, Hematology and Oncology, University Hospital, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Glienke
authors.forename: Kai U
authors.initials: KU
authors.lastname: Chow
authors.forename: Nina
authors.initials: N
authors.lastname: Bauer
authors.forename: Lothar
authors.initials: L
authors.lastname: Bergmann
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology* / Q000627:therapeutic use; D018053:Arsenites / Q000494:pharmacology / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics*; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010087:Oxides / Q000494:pharmacology / Q000627:therapeutic use; D017670:Sodium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D001152:Arsenicals; D018053:Arsenites; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D003598:Cytoskeletal Proteins; D010087:Oxides; D017670:Sodium Compounds; D025721:WT1 Proteins; C484859:WTIP protein, human; C017947:sodium arsenite; D000077237:Arsenic Trioxide