WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant.
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.
Haber
D A
DA
Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center, Boston 02129.
Park
S
S
Maheswaran
S
S
Englert
C
C
Re
G G
GG
Hazen-Martin
D J
DJ
Sens
D A
DA
Garvin
A J
AJ
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*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025721:WT1 Proteins