WT1-Mediated Growth Suppression of Wilms Tumor Cells Expressing a WT1 Splicing Variant

• Published in: Science (American Association for the Advancement of Science) Vol. 262; no. 5142; pp. 2057 - 2059
• Main Authors: Haber, Daniel A., Park, Seon, Maheswaran, Shyamala, Englert, Christoph, Re, Gian G., Hazen-Martin, Debra J., Sens, Donald A., Garvin, A. Julian
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 24.12.1993; American Association for the Advancement of Science
• Subjects: Alternative Splicing; Amino Acid Sequence; Animal tumors. Experimental tumors; Animals; Antimitotic agents; Antineoplastic agents; Base Sequence; Biological and medical sciences; Cell Division - genetics; Cell lines; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Exons; Experimental renal and urinary tract tumors; Genes, Wilms Tumor - genetics; Genes, Wilms Tumor - physiology; HEK293 cells; Humans; Kidney cancer; Kidneys; Medical sciences; Messenger RNA; Mice; Mice, Nude; Molecular Sequence Data; Neoplasm Transplantation; Nephroblastoma; Protein isoforms; RNA, Messenger - genetics; Splicing; Tumor cell line; Tumor Cells, Cultured; Tumors; Wilms Tumor - genetics; Wilms Tumor - pathology; Wilms tumors; WT1 Proteins; Animal model; Urinary system disease; Suppression; Renal disease; Transcription repressor; Malignant tumor; Experimental disease; Phenotype; Etiology; Wilms tumor; Mutation; Tumor cell; Tumor suppressor gene
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.8266105

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.