title: WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
abstract: A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2 sequences, a splicing alteration that was also detected in varying amounts in all Wilms tumors tested but not in normal kidney. Production of this abnormal transcript, which encodes a functionally altered protein, may represent a distinct mechanism for inactivating WT1 in Wilms tumors.
authors.affiliation: Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center, Boston 02129.
authors.forename: D A
authors.initials: DA
authors.lastname: Haber
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Maheswaran
authors.forename: C
authors.initials: C
authors.lastname: Englert
authors.forename: G G
authors.initials: GG
authors.lastname: Re
authors.forename: D J
authors.initials: DJ
authors.lastname: Hazen-Martin
authors.forename: D A
authors.initials: DA
authors.lastname: Sens
authors.forename: A J
authors.initials: AJ
authors.lastname: Garvin
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D016162:Genes, Wilms Tumor / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured; D025721:WT1 Proteins; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology*
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins