Molecular biology

The Wilms' tumour gene (WT1) is a tumour suppressor which resides at chromosome 11p13. The protein encoded by the WT1 gene is a transcriptional repressor that downregulates expression of the insulin-like growth factor II and the insulin-like growth factor I receptor.

Differential splicing of the WT1 transcript results in four isoforms of the final protein.

All isoforms have four zinc finger DNA-binding domains but they have differing sequence specificities.

WT1 is expressed in:

• nephrogenesis - in the condensed mesenchyme, renal vesicle and glomerular epithelium
• the indifferent gonad, eventually being restricted to the Sertoli cells of the testis and granulosa and epithelial cells of the ovary, and the uterus
• WT1 is also one of the molecules that are known to control cellular apoptosis (3)

Reference:

• Breuning, W. et al.. Nature Genetics1992; 1: 144-8
• Skuse GR, Ludlow JW. Tumour suppressor genes in disease and therapy. Lancet 1995;345: 902-6.
• Yang L, Han Y, Suarez Saiz F, Minden MD. A tumor suppressor and oncogene: the WT1 story. Leukemia 2007;21: 868-876.